----------------------- Page 1----------------------Genetics & Its Impact in Medicine & Dentistry

Prof .Dr. Masood Anwar Qureshi, Ph.D Chairman, Department of Physiology, DIMC, Director, IBMS, DUHS October 2013 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 2----------------------Text & Reference Books · · · · · Text: Human Genetics: Concepts and Applications; Ricki Lewis, th McGraw-Hill, 7 Ed., 2007 Emery's Elements of Medical Genetics; Peter Turnpenny's and Sian th Ellard, Elsevier Churchill Livingstone, 12 Ed., 2005 Medical Genetics; Jorde LB, Carey JC, Bamshad MJ, White RL, Mosby, 2006 Medial Genetics. John Bradley, David Johnson, Barbara Pober. 3rd ed., Blackwell Publ., 2006

rd Human Genetics. Gangane, SD, Elsevier, 3 ed., 2008 Reference Books: Genetics: Analysis of genes and genomes. Daniel L Hartl, Elizabeth th W Jones, 5 Ed., ones &Bartlett Publ., 2001 · Genetic Analysis of Complex Diseases. Ed. Jonathan L Haines, Margaret A Pericak-Vance, 2nd Ed., Wiley-Liss, 2006 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., Genetics on Medicine & Dentistry 2013 Prof. Qureshi, DUHS · · · ----------------------- Page 3----------------------Importance of genetics in curricula · · · An increasingly important role in medicine Its teaching be increased proportionally future physicians/dentists should have knowledge of applications of new genetic technology · to understand the associated ethical, legal and social issues · Schools of Medicine and Dentistry should incorporate genetic education into their curriculum in a fully integrated fashion · This model may serve as a template for other medical curriculum still in development Reference:

Robinson & Fong (2008) Genetics in medical school curriculum: A look at the University of Rochester School of Medicine and Dentistry. J Zhejiang Univ. Sci. B. 2008 Jan; 9(1):10-5 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 4----------------------Inter-relationship various factors at birth: involvement of genetics 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 5----------------------Super Boy · A new born with prominent muscular development had ± within 5 yrs twice normal size of muscle (1/2 of normal amount of body fat) ± family history of strongly built relatives; ± body composition suggested to be: · due to parental genes · Absence of myostatin protein

8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013

Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 6----------------------Myostatin · required to stop stem cells from making a muscle too large ± due to a mutation - turns off its function, muscles bulges; individual healthy but may develop problems of heart · Which too has mysostatin · In other species: ± `Double muscling' cattle, naturally occur; high weights early in life ± Chicken breeders for `meatier birds' ± researchers created ` mighty mice' · to study muscle over- growth 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013

Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 7-----------------------

Myostatin: Clinical Applications · Blocking myostatin function helps to understand: ± muscle dystrophy & wasting (AIDS & cancer) ± potential for bodybuilding abuse ± ethical questions like performance enhancement ± myostatin gene variants predict athletic power under proper training ± to improve quality of life in general but also for abuse Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013

----------------------- Page 8----------------------Genetics & Genomics · · · Genetics- inherited traits & their variations Geneology- relationships but not traits Genes; DNA - units of inheritance, specify particular proteins ± these control characteristics ± creates much of individuality · from hair to eye color · from body parts shapes to our talents, personality traits & health Not all DNA encodes protein Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

·

8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013

----------------------- Page 9----------------------· · Traits- characters ± by genes; mostly by environments Genome: ± complete set of genetic information & instruction for characteristics of an organism, · including protein- encoding genes & DNA sequence

· Availability of rapid & relatively inexpensive automated sequencing methods ± made entire genomes base sequenced 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 10----------------------· Genomics: ± new subdiscipline emerged · study of structure & function of whole genome · focus on more common illnesses · influenced by many genes interacting with each

other & environment

8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013

Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 11----------------------Understanding of Medical Genetics · Includes: ± Thalassaemia ± models for mol. genetics ± Autosomal recessive disorders ± Autosomal dominant disorders ± X-linked disorders ± Multifactorial disorders ± Non-traditional inheritance contiguous gene syndromes ± Chromosomal disorders Resources & significance DNA Bank 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 12----------------------Medical genetics · Previously refers to rare conditions (attended by specialists), now forms basis of understanding of most of major diseases ± Includes pediatrics ± & common adult disease e.g CVD, DM, many cancers & many psychiatric disorders · Genes influence all components of human body ± genetic disease relevant to all medical practitioners · Its understanding ± now essential for todays' health care practitioners 8-30am 1st Sem 2013 6th Batch HBMS 701, Nov., 2013 Genetics on Medicine & Dentistry Prof. Qureshi, DUHS

----------------------- Page 13----------------------Medical genetics · · involves ± any application of genetics to medical practice. includes: ± Studies of inheritance of diseases in families ± Mapping of disease genes to specific locations on chromosomes

Qureshi.. DUHS ----------------------. prognoses. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. cancer ± applying `expression panel' which determines which genes are turned on or off in affected cell samples from tumor or from blood · · ± Very useful in diagnosing & treating cancer may prevent. 2013 Genetics on Medicine & Dentistry Prof.. Nov.Page 15----------------------Genetic testing · Gene expression ± refers to cells use of information in DNA sequence to synthesize a particular protein · DNA from cheek lining cells reveal specific gene variants present in all body cells Gradually becoming standard part of health care to identify ± Risk factors/ suspicion for diseases/ · cystic fibrosis & T2DM & CVD. Qureshi.. 2013 ----------------------. Qureshi. control or treat symptoms likely to develop to gain information ± about future pregnancies Genetics on Medicine & Dentistry Prof. & treatments to patients & their families 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. 2013 . Nov.± Analysis of mol mechanisms for genes cause disease ± Diagnosis & treatment of genetic diseases ± Gene therapy · insertion of normal genes into patients to correct genetic disease ± genetic counseling · which involves communication of information regarding risks. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 14----------------------Medical genetics imp for health care practitioner · · Genetic diseases ± Majority of diseases both of pediatric & adult populations Modern medicine ± focuses on importance of prevention of disease process · leads to more effective treatment ± among highest goals of medicine Provide basis ± for understanding of fundamental biological makeup of organisms · leads to a better understanding of disease process Genetics on Medicine & Dentistry Prof. delay.

----------------------... Nov. ii. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. 2013 ----------------------. iv. Qureshi.Page 16----------------------Steps required i.. 2013 ----------------------. Nov. Qureshi. Qureshi.Page 19----------------------· · · Tests kept confidential Laws must prevent employers & insurers from discriminating based on genetic information New strategies needed for insurance procedures on symptoms present before or at the time of request for coverage Genetics on Medicine & Dentistry Prof. DUHS ----------------------. 2013 . Record complete family history Provide cell samples (from inside cheeks) Isolate sample DNA & applied to personalized microarrays Calculate & results communicated Genetics on Medicine & Dentistry Prof. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. 2013 Genetics on Medicine & Dentistry Prof. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.. iii.Page 18----------------------· Identify cancer cells very early ± Can monitor progression of disease & progress of treatment ± Response of tumor cells & individual's immune system to particular drugs ± Selection of drugs to produce intolerable side effects 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 17----------------------Microarrays · DNA chips ± postage stamp-sized pieces of glass or nylon ± with particular sequences of DNA attached ± genes aligned in fixed positions.device called microarrays · shows at a glance which genes a person has ± typical microarray bears hundreds or thousands of DNA pieces ± Fig shows probabilities of developing certain conditions & refining medical diagnosis Genetics on Medicine & Dentistry Prof.

a cell contains 2 genomes of DNA Genomics ± study of genes & their interaction Selection of specific gene tests ± based on family & health history ± to detect or estimate risk of developing certain conditions DNA microarrays ± detect many genes at once ± Expression arrays indicate which proteins a cell makes Genetics on Medicine & Dentistry Prof. Nov. Nov... 2013 Genetics on Medicine & Dentistry Prof. Qureshi. DUHS ----------------------. 2013 ----------------------.----------------------. Qureshi. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 20----------------------Effects of Genes on Health Role of genes established in many types of conditions Types of Disorder or Example Associations Single gene (Mendelian) Chromosomal disorder Complex (multifactorial) Cancer (Somatic mutation) Single nucleotide Polymorphism (SNPs) population Cystic fibrosis Down syndrome Diabetes Mellitus Breast cancer Associated with various conditions in different 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 21----------------------SUMMARY: Genetic Testing · · · · · Genes ± gives instructions to manufacture proteins ± determine inherited traits Genome ± complete set of genetic information. 46 determined ± Lead to cytogenetics · discovery of Down syndrome (1959) ± due to extra copy of 21 chromosome . 48 ± In 1956.Page 22----------------------· Watson & Crick (1950's) ± specification of physical structure of DNA ± · formed basis of molecular genetics · Correct specification of chromosome # ± Since 1920.

Page 25----------------------· Single gene disorders classified ± according to type of inheritance · autosomal dominant · autosomal recessive · sex-linked OMIM ± ± ± ± lists 15000 autosomal 893 sex-linked 56 Y-linked & 64 mitochondrial gnome · most traits are genetic diseases · · Disease causing mutations identified only in 1700 Genetics on Medicine & Dentistry 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 24----------------------Types of genetic diseases · 20. Turner syndrome · Disorders with single gene altered .Page 23----------------------· Significant achievements since 1960 due to technological advancement ± mainly in molecular genetics. DUHS ----------------------. hemophilia · Multifactorial disorders ± Results from combination of multiple genes & environments · many birth defects ± cleft lip &/palate. 2013 Genetics on Medicine & Dentistry Prof. Nov. Nov. 2013 Genetics on Medicine & Dentistry Prof. · Human Genome Project 8-30am 1st Sem 2013 6th Batch HBMS 701.8-30am 1st Sem 2013 6th Batch HBMS 701..mendelian conditions or single gene disorders ± cystic fibrosis. Qureshi. Nov.000-25. . DUHS ----------------------. Qureshi. DUHS ----------------------. many adult disorders ± heart dis ease. 2013 Genetics on Medicine & Dentistry Prof. alteration in these or in combination of them can produce genetic disorders.. sickle cell disease. classified: · Chromosome disorders ± Entire chromosome (or large segments) missing or altered · Down syndrome. Qureshi.. Nov.. diabetes · Mitochondrial disorders ± relative small number of disease caused by · alterations in small cytoplasmic mitochondrial chromosome 8-30am 1st Sem 2013 6th Batch HBMS 701.000 genes.

DUHS ----------------------. 2013 ----------------------.(polydactyly. Qureshi..Page 28----------------------· th 17 century (Leeuwenhoek & de Graaf) ± sperm & ova recognized ± indicating transmission to offspring by female too th th 18 & 19 century ± Pierre de Maupertius · Studied hereditary trait. Nov.. 2013 Genetics on Medicine & Dentistry Prof. 50.000 yrs ago Lack of knowledge ± conception. Qureshi. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 26----------------------· · Multiple genetic disease considered on a continuum At one end ± cystic fibrosis & Duchenne muscular dystrophy · strongly determined by genes At other end ± measles strongly · Strongly determined by environment Lie in the middle ± Prevalent birth defects.000-200. inheritance Aristotle & Hippocrates ± ± human characteristics determined · by semen (produced by whole body) · menstrual blood (culture medium) · uterus (incubator) 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------.Page 29----------------------- . heart diseases & cancer · products of varying degrees of both genetic & environmental influences Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof. hypertension.2013 Prof. Qureshi. reproduction.Page 27----------------------· · · Homo sapiens. Qureshi. DUHS ----------------------. albinism) · pedigree studies showed their inheritance in different ways · 8-30am 1st Sem 2013 6th Batch HBMS 701. DM.. Nov. Nov.

Nov. 2013 Genetics on Medicine & Dentistry Prof.Page 31----------------------Mendel's breeding experiments · Contrasting characters in garden pea Each experiment had varieties differed only in one characteristic When plants with tallness bred to short ones offspring in first filial (F1) generation . 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof. Nov. DUHS ----------------------. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------. Qureshi.Page 33----------------------· Pure-bred plants with 2 identical genes used in initial cross ± now called homozygous .Page 30----------------------- 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.Page 32----------------------· · · · Characters appearing in F1 ± dominant Those reappearing in F2 ± recessive Mendel interpretations of his results entirely correct (even by law of statistics) Proposed ± each character controlled by a pair of factors one inherited from each parent 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.tall Plants of F1 interbred ± both tall & short plants (ratio 3:1) Fig....· · Adams (1756-1818) ± different mechanism of inheritance George Mendel (1822-1884) ± presented breeding experiments on garden pea remained unnoticed till 1900 work considered as discovery of genes & their inheritance 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------. Qureshi. Nov.

Nov.. Genetics on Medicine & Dentistry 2013 Prof.Page 36----------------------Law of Segregation · Each individual possesses two genes for a particular characteristic ± only one can be transmitted at any one time Rare exception to this rule can occur when ± two allelic genes fail to separate ± because chromosome non-disjunction occurred at first meiotic division · . DUHS ----------------------.Page 34----------------------· An alternative method for determining genotypes in offspring involves ± construction of what is now known as · Punnett's square (for studying segregation of genes in large populations) 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 35----------------------Laws of Uniformity · Mendel's experiments lead to 3 main principles ± laws of uniformity ± segregation ± independent assortment · When two homozygous with different alleles are crossed all off spring in F1 generation are identical & heterozygous (characteristics do not blend. Qureshi. DUHS ----------------------.· · Hybrid F1 plants: each has one gene for tallness & other for shortness ± heterozygous Genes responsible for these contrasting characteristics ± allelomorphs or alleles 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. as had been achieved previously. 2013 Genetics on Medicine & Dentistry Prof. Qureshi.. Nov. & can reappear in later generations 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------.

.homozygous Mendel proposed ± each individual has two genes for each characteristic · one is inherited from each parent · one is transmitted to each child ± genes at different loci act & segregate independently Chromosome separation at cell division facilitates gene segregation Genetics on Medicine & Dentistry Prof. Nov.Page 38----------------------Summary: Mendel's Experiments · · · Character manifest in a hybrid (heterozygote)dominant Recessive character expressed only in an individual with 2 copies of gene .. Nov. Qureshi. DUHS ----------------------. Qureshi. 2013 Genetics on Medicine & Dentistry Prof.Page 40----------------------II. Qureshi.. Levels of Genetics: From Genes to Genomes . 2013 ----------------------. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701.`linked' · Law of Mendelian inheritance breached by many other ways.. DUHS ----------------------. Nov. Nov.8-30am 1st Sem 2013 6th Batch HBMS 701. but overall remain foundational to our understanding of science 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 39----------------------- 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 37----------------------Law of Independent Assortment · Members of different gene pairs segregate to offspring independently of one another · In reality this is not always true ± genes close together on same chromosome tend to be inherited together .

level to populations to evolution of species ± DNA ± Genes ± Chromosomes ± Genome ± individuals ± families ± populations · A gene can exist in more than one form. Qureshi. Nov. Gene 1. DNA 3. Family (Mother--I------Father) Population I I Son Genetics can be considered at several levels 8-30am 1st Sem 2013 6th Batch HBMS 701.· Transmission of information from mol. 2013 Genetics on Medicine & Dentistry Prof. Nov. Chromosome (cell) 4. DUHS ----------------------.. or allelle · Comparing genomes among species reveals ± Evolutionary relatedness 8-30am 1st Sem 2013 6th Batch HBMS 701. Human Genome (Karyotype.Page 41----------------------2.. & Dentistry 2013 Genetics on Medicine Prof.32 chromsome) 5. Individual (born child) 6. Qures .

Page 42----------------------Only 1. 2013 Genetics on Medicine & Dentistry Prof. Nov. not all functions of RNA are known Forms basis of definition of gene following genomic information As a sequence of DNA with a known function 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.Page 43----------------------Genes Individual genes vary by small changes in DNA base sequences same protein N-encoding gene may very slightly from person to person Variants of genes called allelle Changes in sequence arise by process called mutations mutated gene passed on to dividing cell change in sperm/egg cell becoming a fertilized egg... Qureshi. DUHS . DUHS ----------------------. harmful causing disease or mostly have no effect at all provide variationfreckled skin useful like having HIV resistant (unable to produce protein that binds HIV.5 % of DNA in human genome encodes protein. DUHS ----------------------. DUHS ----------------------. such people resistant to HIV infection. 2013 Genetics on Medicine & Dentistry Prof. many with no visible effects changed encoded protein does not affect its function 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof.hi. Qureshi. the rest includes many highly repeated sequences of unknown function sequences that turn protein-encoding genes on or off other sequences whose roles yet to be discovered Recent discovery RNA actually controls which proteins a cell manufacturesprocess called RNA interference Likewise.. Nov.Page 44----------------------Can be helpful. Qureshi. passed on to next generation 8-30am 1st Sem 2013 6th Batch HBMS 701.

Page 46----------------------Identification of combinations of SNP's found exclusively among people with a particular disorder and use their patterns to estimate disease risks · Association studies (technique) · examines DNA variants in population & · detects particularly combinations of SNPs as above 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------. Nov.Page 48----------------------Karyotype .many forms More than 3 million Single Nucleotide Polymorphism SNPs. Qureshi. yet no change in person's appearance or health.----------------------. Qureshi.Page 45----------------------· Parts of DNA can vary among individuals.1903) independently to carry hereditary factors or genes Supported ± realization of their behavior at cell division provide an explanation ± for genes segregates Genetics on Medicine & Dentistry Prof... · such a variant in a sequence that is present in at-least 1% of a population . snips Single base site differing among individuals Microarrays can include both disease-causing mutations SNP's that just mark places where people differ 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. body) suggested (Walter Sutton & Theodor Boveri.. 2013 Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof.Page 47----------------------Chromosome · Chromosomal basis of inheritance ± Chromosomes (chroma.polymorphism. Nov. DUHS ----------------------. DUHS ----------------------. color. soma. Qureshi.

Qureshi.Page 49----------------------Cells.· Detect abnormalities. a process called differentiation 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof.Page 50----------------------Muscle cell: produces abundant contractile proteins fibers but not scaly keratins (fill skin cells or collagen & elastin proteincharacteristics of CT cells all three cell types have complete genomes Specialized cells aggregate & interact forming tissues which in turn forms organs & organ systems 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof.. DUHS ----------------------. DUHS ----------------------. Nov.shown by charts ± can `run in families' & sometimes said to be segregating order chromosomes pairs from largest to smallest ± stained with dyes or fluorescent chemicals to create different patterns to highlight abnormalities 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. Nov. Nov..Page 51----------------------Stem Cells Parts of organs made up of rare unspecialized stem cells that can divide to yield another stem cell & a cell . 2013 Genetics on Medicine & Dentistry Prof. tissues & organs: Trillion of cells in human body All cells except RBC contain complete genetic instruction but cells differ in appearance & function because they use only some of their genes.. DUHS ----------------------. Qureshi.

or expressed (Phenotype: visible trait. Qureshi..growth & repair But are controlled. lifting of this control in super boy lead to overgrowth of his muscles 8-30am 1st Sem 2013 6th Batch HBMS 701. refers to underlying instructions). genotypes.. biochemical changes or effect on health) Alleles further distinguished by how many copies it takes to affect phenotype? 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof. Qureshi.Page 53----------------------Individual Alleles present .Page 54----------------------Dominant allele: produces an effect when present in just one copy ( on one chromosome) Recessive allele: must be present on both chromosomes to be expressed alleles on Y chromosomes exception: recessive alleles on X chromosome in males expressed as no second chromosome to block expression 8-30am 1st Sem 2013 6th . DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. Nov.that differentiates Help organs to maintain a reserve supply of cells . Nov.Page 52----------------------these have ability to differentiate further Cell differentiation lead to establishment regenerative medicine replace degenerative cells causing conditions: Parkinson disease Huntington disease Repositories for bone marrow cells & brain cells being established 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------. Nov.. Qureshi.

DUHS ----------------------. Nov. Nov. begins with transmission genetics when an interesting trait or illness in family is recognized Charts called pedigrees represent members of a family & indicate which individuals have particular traits Fig.. 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------.poineered study of single genes using pea plants 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------.. Qureshi.Page 57----------------------Population · Biologically ± a group of interbreeding individuals. · Genetically ± it is a large collection of alleles distinguished by frequency of particular alleles · Swedish people with greater frequency of allele for light hair & skin than people from Ethiopia with dark hair & skin . 2013 Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof.Batch HBMS 701. Qureshi. of levels: shows a pedigree but an unusual one ± a family with identical triplets .Page 56----------------------Molecular genetics studying nucleic acids & proteins. Nov..Page 55----------------------Family Individuals genetically connected to families A person has half his or her genes in common with each parent each sibling and ¼ with each grand parent Firs cousin share 1/8 th of their genes Study of traits in families transmission genetics or Transmission/ Mendelian genetics George Mendel.

These small scale genetic changes foster more obvious species distinctions we most often associate with evolution 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 58----------------------People looking different suffering from different health problems reflect frequencies of distinctive set of alleles All alleles in a population constitute gene pool An individual does not have a gene pool Population genetics very important in application like health care & forensics Also the very basis of evolution Which is defined as changing allele frequencies in populations. Nov.. the most alike their cytochrome a. sequence is (Table) 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. DUHS ----------------------.) · Cytochrome c: most ancient protein helps ± to extract energy from nutrients in mitochondrial respiration ± 20 of 104 amino acids occupy identical positions in cytochrome c of all eukaryotes ± more closely related two species are. Qureshi.8-30am 1st Sem 2013 6th Batch HBMS 701.Page 60----------------------Cytochrome c Evolution Organism · · · · · · · · · Chimpanzee Rhesus monkey Rabbit Cow Pigeon Bullfrog Fruit fly Wheat germ Yeast Number of amino acid differences from Humans 0 1 90 10 12 20 24 37 42 8-30am 1st Sem 2013 6th . Nov. DUHS ----------------------.Page 59----------------------Evolution · More similar sequences are.a. more recently two species diverged from a shared ancestors (Fig... 2013 Genetics on Medicine & Dentistry Prof. Nov.

by 8 a. Nov. Genome comparisons can clarify our kinship with other species Genetics on Medicine & Dentistry Prof. Nov. 2013 Genetics on Medicine & Dentistry Prof.01 % of our genes Two members of different races may have more genes in common than of same race Very few. 2013 Genetics on Medicine & Dentistry Prof. Qureshi.Page 61----------------------· For example. defined by fewer than 0. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701. 12 a. Qureshi. DUHS ----------------------.Page 62----------------------· Human share more than 98% of DNA sequence with chimpanzee ± difference largely in organization of genes & number of copies than in overall sequence Learning functions of human specific genes may explain ± differences between us & them · e.a. DUHS ----------------------.. 2013 Genetics on Medicine & Dentistry Prof.Batch HBMS 701.Page 63----------------------8-30am 1st Sem 2013 6th Batch HBMS 701. human cytochrome differs ± from horse cytochrome c by ± from kangaroo cytochrome c ± human protein identical to c. 2013 ----------------------. lack of our hair & use of spoken language.g.. Qureshi.a. Nov. gene variants are unique to any one · · · · . Qureshi. Nov. DUHS ----------------------. that of chimpanzee · Genome sequence comparison reveal ± more about evolutionary relationships than comparing single genes 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 64----------------------Race · Polymorphic studies of variety of ethnic groups indicate ± arisen of modern human from Africa ± gene pool of all groups are subsets of modern African gene pool Is social concept & not biological ± agreed by both biologists & geneticists race (defined by skin color In fact.. if any..

Much of the genome does not encode protein · Variants of a gene.Page 66----------------------· · · · · · Human genome contains about 3 billion DNA bases Cells differentiate by expressing subsets of genes Stem cells divide to yield ± other stem cells & cells that differentiate Pedigrees: ± diagrams use to study traits in families Genetic populations ± defined by their collection of alleles . Qureshi.allele arsis by mutation. 2013 Genetics on Medicine & Dentistry Prof. A polymorphism is a site or sequence of DNA that varies in one person or more of a population. Alleles may be dominant (exerting effect in a single copy) or recessive 9requirung two copies for expression) · Chromosomes consists of DNA and protein..they might differ slightly from one another but encode same protein.g polydactyly & albinism ± Color blindness & hemophilia now referred to as sexor -X-linked .. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 67----------------------The Origins of Medical Genetics · Curiosity aroused by familial conditions e. Qureshi. Qureshi. An annele combination constitutes the genotype.. RNB carries the gene sequence information so that it can be utilized while the DNA is transmitted when the cell divides. DUHS ----------------------. The phenotype is the gene's expression.Page 65----------------------SUMMARY Levels of Genetics: · Genes encode proteins and the RNA molecules that carry out protein synthesis. DUHS ----------------------.termed gene pool Genome comparisons among species ± reveal evolutionary relationships Genetics on Medicine & Dentistry Prof. X & Y sex chromosomes bear genes that determine sex 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof. Nov. Nov. Nov. 2013 ----------------------.racial or ethnic group 8-30am 1st Sem 2013 6th Batch HBMS 701. 22 types autosomes do not include genes that specify sex.

were speculated for mechanisms causing these disorders · During 1900 Mendel's work resurfaced ± (DeVries. 11031 established gene loci & 8784 gene map loci established Genetics on Medicine & Dentistry Prof. in addition to alkaptonuria · By 1966 almost 1500 single-gene disorders /traits identified th · · McKusick published a catalog.. Nov. Nov.inheritance.. Nov. Correns. 2013 ----------------------.trisomy . DUHS ----------------------. former still as daltonism (John Dalton). DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. 12 edition listed 8500 entries (accessible on OMIM.Page 70----------------------· Several rare conditions featuring ± learning difficulties and abnormal physical features are due to · loss of such a tiny amount of chromosome material that no abnormality can be detected using even the most high powered LM- . Qureshi. Online Mendelian Inheritance in Man) By 2003.Down syndrome) · Banding techniques (1970) enabled ± identification of individual chromosomes · Gain/loss of its very small segment ± adverse effect on human development 8-30am 1st Sem 2013 6th Batch HBMS 701.related to study to inherited diseases Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof.Page 69----------------------Chromosomal abnormalities · 1959: identified chromosomal numerical disorder (additional 21chromosome. Qureshi. 2013 ----------------------. Von Tschermak) ± marked real beginning of medical genetics .Page 68----------------------Single Gene Disorders · Albinism & cytinuria ± identified as recessive inheritance. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi..

Qureshi. intelligence. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 73----------------------· Confirmed. each exerting a small additive effect. Alzheimer disease · Genes at several loci interact to ± generate a susceptibility to the effect of adverse environmental trigger factors 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.Page 71----------------------Multifactorial disorders · Frances Galton: ± human characteristics ± stature. ± as a means of estimating the degree of resemblance between various relatives The concept used to explain such parameters like height and color could be determined by ± interaction of many genes. physique.Page 72----------------------· This model of quantitative inheritance ± adapted to explain pattern of inheritance for many common diseases like ± Congenital malformations ±cleft lip and palate. Nov. research based on identical twins.many genes involved in most of these onset disorders .. Qureshi. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------. Introducing concept of regression coefficient. DUHS ----------------------. Qureshi.· conditions as micro-deletions syndromes and are diagnosed using a technique ± FISH (fluorescent in-situ hybridization) ± which combines conventional chromosome analysis (cytogenetics) with much newer DNA diagnostic technology .differences in these parameters must be largely result of environmental influences. DM. Nov. in a non-additive fashion Genetics on Medicine & Dentistry Prof.. late-onset conditions e. 2013 ----------------------.molecular genetics) Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof.g hypertension. in contrast to single-gene characteristics in which action of one gene is exerted independently..

..Page 75----------------------Definitions · Incidence ± Rate at which new cases occur · Prevalence ± Proportion of a population affected at anyone time · Frequency ± Lack scientific specificity but synonymous with incidence when calculating gene frequencies · Congenital ± Condition present at birth. Nov. not all disorders are congenital in terms of age of onset (Huntington disease).± although progress in identifying specific susceptibility loci has been very slow · In some conditions like DM Type1 ± different genes can exert major or minor effects in determining susceptibility Overall mutlifactorial/polygenic ± now known to make a very major contribution to chronic illness in adult Genetics on Medicine & Dentistry Prof. 2013 ----------------------. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. nor are all congenital abnormalities genetic in origin (e. Nov. ± during mitosis. single gene mutations can occur.Page 74----------------------Acquired Somatic Genetic Diseases · Not all genetic errors are present from conception. Qureshi. DUHS · · · 8-30am 1st Sem 2013 6th Batch HBMS 701. · due to DNA copy errors and numerical chromosome abnormalities to arise as a result of errors in chromosome separation Accumulation of somatic mutations and chromosome abnormalities ± are now known to play a major role in causing cancer Probably explain rising incidence with age of many other serious illnesses & aging process Necessary to realize that ± not all diseases with genetic basis is hereditary Genetics on Medicine & Dentistry Prof.g fetal disruptions) 8-30am 1st Sem 2013 6th Batch HBMS 701. ± billions cell divisions occur during life time. 2013 ----------------------. Qureshi. Nov. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ..

. DUHS ----------------------.Page 77----------------------· List & description of all known single-gene traits & disorders /Mendelian inheritance in humans (following laws of transmission · All Gene sequencing revealed ± redundant entries in this list of disorders whose actual number may be 1100 8-30am 1st Sem 2013 6th Batch HBMS 701.. Qureshi. Genes Usually Do Not Function Alone · Inherited traits determined by ± one gene (Mendelian) ± or specified by one or more genes & environment (multifactorial) Even expression of single gene effected ± to some extent. Nov. Qureshi. Nov.----------------------. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof.Page 79----------------------· · Some illness occur in different forms. DUHS · · · 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof. 2013 ----------------------. Nov. Nov. Qureshi. Qureshi. by actions of other genes Idea of modification of genes by environment ± counters genetic determinism ± ± idea that an inherited trait can not be modified Genetics on Medicine & Dentistry Prof. Mendelian or multifactorial Usually inherited forms rarer ± Alzheimer disease ± breast cancer & ± Parkinson disease Genetics on Medicine & Dentistry Prof.Page 78----------------------· Genetics extremely complicated than a one-gene-one disease paradigm · Most genes do not function alone but · influenced by ± action of other genes & ± sometimes environmental factors around with several determinants .called multifactorial 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 76----------------------III.. 2013 . Inherited or not.. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.

Nov. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. Qureshi.Page 83----------------------· · Prediction recurrence risk of a trait or illness can be done ± if its transmission via mendelian/ multifactorial nature is studied (as fro BRACA 1 for breast cancer) Environmental factors may also affect gene's expression ± exposure to pesticides mimicking estrogen effect may .Page 82----------------------· In jewish families of Eastern European descendents (Ashkenazim) with many members affected at young age inheriting ± most common BRCA 1 mutation confers on 86% chance of developing disease over a lifetime but women from other ethnic groups who inherit allele ± may have only 45% chance Perhaps different alleles of other genes ± interact with BRCA1 in different populations · · 8-30am 1st Sem 2013 6th Batch HBMS 701.. DUHS ----------------------. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------.. Nov. Qureshi.Page 80----------------------· Drugs to lower cholesterol level ± developed from work on 1 million children with familial hyper-cholesterolemia (OMIM 144010) · Knowledge about nature of a trait or illness (Mendelian or multifactorial) imp for predicting risk of recurrence · Probability of a Mendelian trait occur in another family member ± simple to calculate using laws of Mendel 8-30am 1st Sem 2013 6th Batch HBMS 701.----------------------.. predicting recurrence of a mulifactorial trait ± difficult because of several contributing factors One form of inherited breast cancer illustrates ± that gene rarely acting alone. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. can complicate calculation of risk Mutations in a gene called BRCA1 cause fewer than 5% of all cases of breast cancer (OMIM 113705) ± but studies of diseases in different populations have confusing results Genetics on Medicine & Dentistry Prof.Page 81----------------------· · · In contracts. Nov.

Page 86----------------------Mendelian & Multifactorial Genetic Disorders Mendelian disorders Multifactorial Disorders Achodroplasia Breast cancer Cystic fibrosis Bipolar effective disorders Duchenne muscular dystrophy Cleft palate Hemochromatosis Dyslexia Hemophilia Diabetes mellitus Huntington disease Hypertension Neurofibromatosis Migraine Osteogenesis imperfecta Neural tube defect Sickle cell disease Schizophrenia Tay sachs disease Seizure disorders 8-30am 1st Sem 2013 6th Batch HBMS 701. NY. Nov. Genetics on Medicine & Dentistry .Page 84----------------------· · BRCA1 cancer prevalent in Long island. DUHS ----------------------. Nov... Qureshi. Nov. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701.population ± includes both many Ashkenazim & many people exposed to pesticides Predictions of inherited diseases considered ± in terms of `modified genetic risks' which takes into account single genes as well as environmental & family background information A modified genetic risk necessary ± to predict BRCA1breast cancer occurrence in a family Genetics on Medicine & Dentistry Prof..Page 85----------------------Inherited trait considered unchangeable ± (an individual trait inevitable) ± called genetic determinism Harmful socially one ethnic group labeled genetically less intelligent than other one Lowered expectations & fewer educational opportunities for those perceived as biologically inferior Environment has a huge impact on intellectual development (Questions of bioethics?) 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. Qureshi.. Nov. DUHS ----------------------. 2013 ----------------------. 2013 Genetics on Medicine & Dentistry Prof.cause breast cancer (very difficult to separate genetic & environmental contribution) 8-30am 1st Sem 2013 6th Batch HBMS 701.

. ± with increasing recognition of role of genetic factors in causing illness at all ages . 2013 ----------------------..Page 88----------------------SUMMARY: Most genes do not function alone · · · Single gene determine Mendelian traits Multifactorial traits reflect influence of one or more genes & environment. ± predicting recurrence of a multifactorial trait is more difficult Genetic determinism± idea that expression of an inherited trait can not be changed Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.2013 Prof. Qureshi. Nov. DUHS ----------------------.Page 89----------------------The Impact of Genetic Disease · 20th century saw improvement in ± all areas of medicine ± public health ± therapeutics · resulting in ± changing patterns of disease. Recurrence of a Mendelian trait is predicted ± based on Mendel's laws.Page 87----------------------Current View · Genes at several loci interact to generate a susceptibility to effects of adverse environmental trigger factors · Many genes involved in most of these adult onset disorders · In some conditions like T1DM different genes can exert major or minor effects in determining susceptibility · Overall multifactorial / polygenic conditions known to make a major contribution to chronic illness in adult life 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------. Qureshi. Qureshi.

2013 Genetics on Medicine & Dentistry Prof. Nobel prize for medicine and/or physiology won 18 times by scientists working in human & molecular genetics or related fields.. project run 1990-2005. · Possible introduction of DNA-based vaccines for conditions such as malaria 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. 3000 base pairs sequence completed by 2000 & complete sequence announced in 2003 prospect of gene therapy represents ± major initiatives that will revolutionize management & treatment of genetic diseases Genetics on Medicine & Dentistry Prof. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.at forefront of medical research ± Human genome project .at forefront of medical research Funded in 1988. DUHS ----------------------. genetics . DUHS ----------------------. Nov.8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.Page 90----------------------Major New Developments · Widely acknowledged & exciting influential area of medical research around genetics & its role in human diseases · Since 62 following Watson & Crick's discovery of DNA structure..Page 93----------------------· Mol.. $ 3 billion to sequence entire human genome (ethical & social implications as well). Qureshi. Qureshi. Nov. 2013 Genetics on Medicine & Dentistry Prof. Nov. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------. Qureshi..Page 92----------------------The Human Project · · · · · Molecular genetics .Page 91----------------------· Thriving molecular technology industry with applications as: · Development of genetically modified diseaseresistant crops · The use of genetically engineered animals to produce therapeutic drugs.

2013 Genetics on Medicine & Dentistry Prof.000 coding genes (blue print for human life).· funded in 1988 · entire human genome sequenced by 2003 · More than $ 3 billion (ethical & social implications as well) ± prospect of gene therapy · Represents major initiatives ± that will revolutionize · management · & treatment of genetic diseases 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 96----------------------Gene Therapy · Most genetic disease resistant to conventional treatment. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. Limited to rare immunological disorders Conditions like cystic fibrosis face problems: ± Targeting correct cell populations ± Overcoming body's natural defense barriers ± Identifying suitable non-immunogenic vectors · 8-30am 1st Sem 2013 6th .Page 95----------------------· Understanding of gene expression will lead to development of new strategies for prevention & treatment of both single gene & polygenic disorders Rapid RNA sequences technologies currently under development will extend range & ease of genetic testing (important ethical & social implications) Genetics on Medicine & Dentistry Prof. Qureshi.Page 94----------------------· · · Originally thought of 100. Qureshi. Genetics on Medicine & Dentistry 2013 Prof. DUHS ----------------------. Nov.000 Many genes perform multiple functions ± make disease classification more complicated Better diagnose & counseling for families with a genetic disease 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.. DUHS ----------------------. current estimates at around 30.. 2013 ----------------------. Nov. Qureshi.. possibility of successfully modify genetic code.

skin ± hair brushes. Nov. DUHS ----------------------. tooth brushes & clothing of missing people. teeth collected from scene to hair. Many court cases of murder. Nov. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. paternity reopened & decided on DNA testing. Nov. DUHS ----------------------.called DNA profiling: many applications very useful in forensics establishing paternity DNA typing can exclude an individual from being biologically related to someone else or from criminals). · After 9/11. DUHS ----------------------. Qureshi.Page 98----------------------V.. Finger printing in human & agriculture identities Understanding certain historical events/ facts 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. & to DNA samples from relatives · DNA profiling -used on a larger scale to identify ± victims of tsunami (Asia. investigations compared DNA sequences in samples of ± bone.Batch HBMS 701. Qureshi. Nov..g cystic fibrosis & Duchenne muscular dystrophy greatly enhance research opportunities Universal optimism: good prospects for successful gene therapy in short-to-medium term 8-30am 1st Sem 2013 6th Batch HBMS 701.2004) & hurricane 8-30am 1st Sem 2013 6th (USA. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------..Page 99----------------------· Rarely media reported DNA profiling prior to 9/11. Genetics on Medicine & Dentistry 2013 Prof.2005) Batch HBMS 701.Page 97----------------------Availability of mouse models for genetic disorders e.Page 100----------------------- . raping. 2013 Genetics on Medicine & Dentistry Prof. Applications of Genetics In diverse areas: Establishing identity & origins Matching DNA sequence can clarify relationship ± the approach..

2013 ----------------------..· · · DNA data bases established for ± convicts/criminals/suspects in UK. & ± add an unprecedented precision & personalization to health care Genetics on Medicine & Dentistry Prof. The Lemba. Qureshi. The Lembo practiced Judaism long before DNA analysis became available Genetics on Medicine & Dentistry Prof. Qureshi. Russia.Page 101----------------------· Rewriting history: example: Thomas Jafferson ± his family's unusual Y chromosome matched that of descendents of Eston Hemings & supported · that either the president. a son of slave. · Sally Heming.Page 102----------------------National Genetic Database · Attempts to record genetic & other types of health information on citizens in hope of better health benefits with new treatments Problems in future? Raised by bioethicists ± How will the information be used? ± Who will have access to it? ± How can people benefit from the project? If all reservations are met ± human genome information will working of human body at molecular level. Nov.Page 103----------------------- . Korea. DUHS ----------------------. 2013 ----------------------. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. his brother or one of his · nephews fathered Eston Heming. Nov... Nov. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701. Virginia May provide wrong evidence ± planted/politically motivated Helps adopted individuals ± locate their blood relatives (specially in USA from China. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. S. adopted individuals can provide a DNA sample & search database by country of origin 8-30am 1st Sem 2013 6th Batch HBMS 701. a modern people with dark skin: ± have the same Y chromosome DNA sequence as cohanim. a group of jewish priests. Guatemala.

ukbiobank.php?show=main&lang=engl Genome EUtwin Europe http>//www.uk/ 8-30am 1st Sem 2013 6th . together with pertinent clinical details and extensive references Electronic technology can hope to match the explosive space of development in all areas of genetic research Genetics on Medicine & Dentistry Prof.fi/ UK Biobank UK http://www. location and pattern of expression For the clinician OMIM offers ± a full account of the imp.Page 104----------------------Population Biobanks · Many nations are recording scrutinizing ± genetic ± geneological ± lifestyle ± & health information on their citizens to discover & archive inherited & environmental influences on common disorders But many questions? ± Who will have access to these? ± How can people benefit from it? ± How might it be abused? There must be criteria agreed by all nations First done by Iceland in 1998 Genetics on Medicine & Dentistry Prof.geenivaramu.Page 105----------------------The First Biobanks · · · · · · BIOBANK Population CARTaGENE Canada http://www.helsinki.genomeutwin.qc. DUHS · · 8-30am 1st Sem 2013 6th Batch HBMS 701.cartagene. Nov. genetic aspects of all Mendelian disorders. together with details of its sequences.ee/ Foundation index. Qureshi. 2013 ----------------------.. Qureshi. DUHS · · · 8-30am 1st Sem 2013 6th Batch HBMS 701.ca/en/ DeCODE Genetics Iceland Website http://www.com Estonian Genome Estonia http://www.· For basic scientists such databases enable ± rapid determination of whether a particular gene has been cloned.ac. Nov.decode. 2013 ----------------------..

genes. Nov.Page 107----------------------- 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 106----------------------· All Human Genome Project data & related information available on the Web · Gene Gateway a new non-technical online guide ± public understanding increase ± Access to genome science resources ± Introduces various tools applied to investigate genetic disorders. Nov. 2013 Genetics on Medicine & Dentistry Prof. chromosomes..Batch HBMS 701. & molecular structures 8-30am 1st Sem 2013 6th Batch HBMS 701. sequence data. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. 2013 Genetics on Medicine & Dentistry Prof.Page 109----------------------Applications of Genomics · Functional Genomics Techniques ± Study of expression of all genes in an Organism · One approach to functional genomics ± ± to create DNA microarrays or DNA chips. DUHS ----------------------. Qureshi.Page 108----------------------Microbial genomics ± Rapidly detect & treat pathogens (disease causing microbes) in clinical practice ± Develop new energy sources ± Monitor environments to detect pollutants ± Protect citizenry biological & chemical warfare ± Clean up toxic waste safely & efficiently 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. genetic variants. Nov. Nov... genome maps.. . 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------. Qureshi. DUHS ----------------------.

2013 Genetics on Medicine & Dentistry Prof. Nov. Qureshi. used an exon trap to identify gene itself · Mutation that causes disease ±an expansion of a CAG repeat from normal range of 11.Page 111----------------------Examples of use of functional genomics · Huntington Disease · Cystic fibrosis · Using RFLP's geneticists mapped its gene (HD) to a region near end of chromosome 4 · Later. it should be show that it is expressed in tissue (s) affected by disease It is mutated in individuals with disease & a wild type version of gene cab cure defect in diseased cells · 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. Nov.. DUHS ----------------------.34 copies to abnormal range of at least 38 copies 8-30am 1st Sem 2013 6th Batch HBMS 701.. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. respectively 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov... 2013 Genetics on Medicine & Dentistry Prof. Qureshi. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof.Page 112----------------------Bioinformatics · Building & manipulation of biological database · Most complex of these databases contain DNA sequences of genomes · Bioinformatics . DUHS ----------------------.holding thousands of cDNA or oligonucleotides. Nov.essential to understanding expression of patterns of complex genomes 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.Page 110----------------------· To implicate a gene as a causative agent in a disease. it must be first be shown that ± It lies close to a marker linked to diseased state ± Later.Page 113----------------------- .

000 protein-encoding genes. for which best method ± available tool .Page 116----------------------· Severe hereditary biochemical defects detected prenatally ± through analysis of fetal biopsies · Genetic basis of many common conditions e.gov/entrez/query.nih.proteomics Current research in proteomics requires ± first that proteins be resolved on a ± massive scale. Qureshi.nim.2-D gel electrophoresis Genetics on Medicine & Dentistry Prof.abundant of contractile proteins ± Skin cells ± scaly proteins-keratins ± Human genome encodes 24.g. DUHS ----------------------.fcgi?db=OMIM) .Page 115----------------------Genetic Diseases · Carrier status for life threatening recessive genetic diseases like CF can be determined in prospective parents · Accumulated information from direct investigation of human genes made possible r-DNA technology provided basis of many diseases 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. DUHS ----------------------..Page 114----------------------Proteomics · · · · · Sum of all RNAs produced by an organism ± its transcriptome Study of these transcripts . Qureshi.. Nov. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------. 2013 Genetics on Medicine & Dentistry Prof. http:/www. Qureshi. Nov.transcriptomics Sum of all proteins produced by an organism ± ± its proteome Study of these proteins. 2013 Genetics on Medicine & Dentistry Prof. each disease carries a number 8-30am 1st Sem 2013 6th Batch HBMS 701.Proteomics · Study of protein types in a particular cell ± Muscle cell.ncbi. hypercholesterolemia showed it ± as part of complex multigenic systems . These involved in disorders or traits ± available on database ± OMIM-Online Mendelian Inheritance in Man (National Center for Biotechnology Information..

Qureshi. 2013 Genetics on Medicine & Dentistry Prof. 2013 Genetics on Medicine & Dentistry Prof. 2013 ----------------------. new gene inserted & cells are then replaced · In in-vivo delivery ± gene targeted directly to patient's tissues. DUHS ----------------------.. · Amniocentesis ± performed between 14 &17 weeks' gestation.Page 118----------------------· Chorion ± a layer of fetal tissue that · spreads over uterine wall during early pregnancy · It can be biopsied after 9th week gestation. 2013 Genetics on Medicine & Dentistry Prof. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. Qureshi.. DUHS ----------------------. Nov.Page 119----------------------Gene delivery · In ex vivo delivery ± cells taken from a patient.· Future will provide ± instances of genetic engineering & corrections of mutations Genetics on Medicine & Dentistry Prof. Qureshi.Page 120----------------------- .. Nov.Page 117----------------------· DNA for prenatal diagnosis is usually obtained from fetus by ± amniocentesis ± or chorionic villus sampling. DUHS ----------------------.. either ± through vagina & ± cervix or across abdominal wall 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. ± involves aspiration of amniotic fluid from around fetus · using a needle passed through abdominal wall 8-30am 1st Sem 2013 6th Batch HBMS 701. usually by infecting them · with a virus which contains new gene 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.

Page 121----------------------The Molecular Medicine team Other Health workers ternist Family Physician Support Group Laboratory Scientist PATIENT. relative contribution by components around family/patient would depend on underlying disorder. Qureshi. FAMILY Geneticist in Counsellor Assembled to deal with a mol. Nov. 2013 Genetics on Medicine & Dentistry Prof. genes involved in lipid metabolism are important candidates in trying to understand polygenic inheritance of cardiovascular disease 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------. Primary care (family) physician & community support groups play key role as health professionals & others will have closet contact with patients & their family 8-30am 1st Sem 2013 6th Batch HBMS 701.-based clinical problem.Candidate genes · · Genes that might be expected to be involved in development of a multifactorial disease For example. DUHS ----------------------.Page 122----------------------Disease with genetic component Map Clone gene Diagnostics ding basic defect Preventive medicine Pharmaco -genomics Gene therapy Drug Understan biologic . Nov. 2013 Genetics on Medicine & Dentistry Prof.. Qureshi..

2013 Genetics on Medicine & Dentistry Prof.therapy 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS Understanding biologic def ----------------------. Qureshi.Page 123----------------------- Disease with genetic component Map Gene(s) to specific chromosomal regions identify genes (Clone gene) Diagnostics basic ect Preventive medicine Pharmaco-genomics Gene therapy Drug therapy 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 125----------------------- Health Care: Genomics changing face of healthcare to integrate new genetic knowledge & technology into patient care.. physicians considered genetics limited only to rare single gene disorders Now. 2013 Genetics on Medicine & Dentistry Prof.. they realize its importance not only in many common conditions but also in how people react to medications . 2013 Genetics on Medicine & Dentistry Prof.. DUHS ----------------------. Nov.Page 124----------------------Steps Involved in the Genetic revolution in Medicine · Uncovering genetic contributions to illness: accomplished by cloning genes for disease with use of tools of human Genome project · Identification of contributing genes & diseasepredisposing variants followed by development of diagnostic tests to predict future risks (tests effective when preventive strategy available · Pharmacogenetics ± prediction of responsiveness to drugs · Development of new gene therapies & drug therapies ± many decades of intensive research 8-30am 1st Sem 2013 6th Batch HBMS 701. Previously. Qureshi. DUHS ----------------------. Nov. Qureshi. Nov.

Nov.Page 126----------------------Inherited illnesses (due to a single gene) distinctive from others Can predict recurrence risk in other family members Presymptomatic testing is possible Different populations may have different characteristic frequencies Correction of underlying genetic abnormality may be possible ±potential of gene therapy Genetics on Medicine & Dentistry Prof. DUHS ----------------------.g perinatal mortality..Disease now seen as due to complex interaction among genes & environmental factors 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof.Page 127----------------------For some parameters e.Page 129----------------------- . Qureshi. DUHS ----------------------... Nov. have declined 8-30am 1st Sem 2013 6th Batch HBMS 701. actual numbers of cases with exclusively genetic causes have probably remained constant but their relative contribution to overall figures have increased as other causes such as infection. overall contribution of genetics increased ± as greater life expectancy provides more opportunity for adverse environmental & genetic interaction to manifest itself For example. DUHS · · · · 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 Genetics on Medicine & Dentistry Prof.. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. Nov. DUHS ----------------------. Qureshi.Page 128----------------------· For other conditions (chronic diseases of adult life). coronary heart diseases & DM ± A few examples can show incidence of genetic disorders & their impact on health at all ages · 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. 2013 ----------------------. Nov.

Predictive testing is possible: all genes present in all cells. Nov.· · By the age of 25. Different populations may have different characteristics frequencies: inherited disorder may be much more common in some populations than others a dozen disorders are much more common among Ashkenazim 4.. Nov. even not expressed. beginning of predictive medicine. 2013 ----------------------. DUHS ----------------------. in case of BRCA1.g coronary artery occlusion & hypertension. Qureshi. Qureshi. 5% of population will have a disorder in which genetic factors play an important role Taking into account genetic contribution to cancer & CV diseases e. Nov. Correction of underlying genetic abnormality may be possible 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 132----------------------- . single gene disorders by Laws of Mendel. 2013 Genetics on Medicine & Dentistry Prof. less predictable in case of infectious diseases 2.Page 131----------------------3. many may have inherited the variant & could be expressed due to environmental interaction 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi. One can predict recurrence risk in other family members . DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701.. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------.Page 130----------------------How Genetic Diseases Differ from Other Diseases 1.. estimation of over 50% of older adult population in developed countries will have a genetically determined medical problem Genetics on Medicine & Dentistry Prof.

. 2013 Genetics on Medicine & Dentistry Prof. Qureshi. cost. compared to infectious diseases which requires a pathogen passed from one person to another) In some situation. DUHS ----------------------.Page 135----------------------· Tests can identify 1. but cells taken from inside cheeks or from blood can reveal a mutation Such genetic information can be considered along with symptoms in redefining a diagnosis But value of predicting an untreatable disease like Huntington is debatable as it causes personality changes & worsens uncontrolled physical movement 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov. cystic fibrosis affect Respiratory system & pancreas.Page 134----------------------· Characteristics frequency in different populations (certain inherited disorders are much more common among certain population groups than others) It is therefore advisable to suggest costly genetic screening tests only to those in which detectable gene variant is fairly common · 8-30am 1st Sem 2013 6th Batch HBMS 701.000 single gene disorders but few follow it. DUHS ----------------------.. DUHS ----------------------.Page 133----------------------For example. Genetics on Medicine & Dentistry . 2013 Genetics on Medicine & Dentistry Prof.. Qureshi. Nov. Nov. 2013 Genetics on Medicine & Dentistry Prof.Recurrence risks predictable (by laws of inheritance. even though not expressed in every cell) 8-30am 1st Sem 2013 6th Batch HBMS 701.. Qureshi. Nov. inherited illness (causative mutation) is predictable prior to symptoms appearance as genes causing problem present in every cell from conception. fear of employment/ promotion/ misuse in insurance industry (genetic discrimination: Laws needed) · It can help people to acquire lifestyle according to predictive testing/ reproductive decisions/ technologies/few for treatment ( like providing clotting factor to a person with bleeding disorder/ possibility of gene therapy in future treatments) 8-30am 1st Sem 2013 6th Batch HBMS 701.

2013 Genetics on Medicine & Dentistry Prof.. gene causes worm to have seizures.preimplantation genetic diagnosis . ± its 302-celled brain much simpler to have coils.Page 139----------------------· · People knowing about their inherited diseases are careful in not having children themselves or donating sperm or ova A technique . may not yet be proven very successful) 8-30am 1st Sem 2013 6th Batch HBMS 701. Qureshi.Page 138----------------------Gene therapy Genetic diseases also differ from others it can sometimes be treated by gene therapy (which replaces a malfunctioning gene in affected parts. shortened lifespan.. ± it lacks a key `motor molecule' that normally shuttles cell contents to appropriate places ± Researchers now focus on this molecule to discover how similarly misguided nerve cells in human embryo's forming brain lead to lissencephaly 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 136----------------------· Use of animal models ± as genetic disease research on humans unethical · Lissencephaly (OMIM 607432): ± brains of affected children lack characteristics coils of cortex region causing severe mental retardation. Qureshi. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. case of hemophilia patient with gene therapy.. DUHS ----------------------. Nov. Nov. Nov. DUHS ----------------------. · difficult to experiment on human embryo or fetuses · Use of roundworm caenorhabditis elegans ± It has a gene very similar in DNA sequence to human lissencephaly gene 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------.2013 Prof. Qureshi. seizures.Page 137----------------------· When mutant.

DUHS ----------------------. which they can pass on to others 8-30am 1st Sem 2013 6th . & allows couples to choose mutation free to complete development in uterus.Page 141----------------------Genetics from a Global Perspective · Genetic faces issues which parallel scientific progress ± ± equal access to testing ± misuse of information ± abuse of genetics to intentionally causing harm · Genetics & genomics achievements may vastly improve quality of life ± (costly.. DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701. DUHS ----------------------.. 2013 Genetics on Medicine & Dentistry Prof.even lacking basic vaccines & medicine 8-30am 1st Sem 2013 6th Batch HBMS 701. not widely available & economically & politically stable nations can have genome based individualized healthcare ± cadillac medicine ± While others just trying to survive . 2013 ----------------------. Nov. Qureshi.Page 140----------------------· Another alternative ± ± to have a fetus tested to determine inheritance of mutant allele. 8-30am 1st Sem 2013 6th Batch HBMS 701. Nov.Page 142----------------------· African nation: ± 2/5 suffer from aids & may die from other infectious diseases · Newborn screening for rare single-gene disorder hardly seems practical · Genetic disorders weaken people ± so that they become more susceptible to infectious diseases.screens 8-celled embryos (lab dish).. Nov. Qureshi. Qureshi. Genetics on Medicine & Dentistry 2013 Prof. One's with devastating illnesses may prompt parents ± to terminate pregnancy ± or may enable parents to prepare for birth of a disabled or ill child Genetics on Medicine & Dentistry Prof.

DUHS ----------------------.Batch HBMS 701. Qureshi. · Some inherited disorders are more common among certain populations groups · Gene therapy attempts to correct mutations 8-30am 1st Sem 2013 6th Batch HBMS 701..Page 144----------------------SUMMARY: Applications of Genetics · DNA profiling can establish ± identity. Genetics on Medicine & Dentistry 2013 Prof. Qureshi.Page 143----------------------· · · Human genome information can ultimately benefit everyone..sequence of both human and mosquito available ± it certainly has clues that researchers can use to develop new type of anti-malarial drugs UN & WHO considering strategies to share new diagnostic tests and therapeutics that arise from genome information Genetics on Medicine & Dentistry Prof. ± DNA collected from habitats used to reconstruct ecosystem 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 145----------------------· Studying genes & genomes of non-human animals can help us ± understand causes of human diseases · Genetic information can be misusd · Agriculture is selective breeding · Biotechnology ± use of organisms or their parts for human purposes · A transgenic organism ± harbors a gene or genes from a different species · In metagenomics. Nov. Qureshi. 2013 Genetics on Medicine & Dentistry Prof. DUHS ----------------------.. presently. Qureshi.. Nov. 2013 Genetics on Medicine & Dentistry Prof. Nov. DUHS ----------------------. Nov.500 drugs . ± Relationships ± and origins · In inherited diseases ± recurrence risks are predictable & mutation may be detected before symptoms arise.Page 146----------------------- . DUHS · 8-30am 1st Sem 2013 6th Batch HBMS 701.genomic information from human & our pathogens & parasites revealing new drug targets malaria ±an infectious disease ± due to female mosquito bite. 2013 ----------------------.

Page 148----------------------Genetic Terminologies Term · · · · · · · · · · Allele Autosome Chromosome Dominant Gene Gene Pool Genome Genomics Genotype Karyotype Definition An alternate form of a gene. Genes at different loci act & segregate independently Chromosome separation at cell division ± facilitates gene segregation Genetics on Medicine & Dentistry Prof. DUHS · · · 8-30am 1st Sem 2013 6th Batch HBMS 701. comparison of genomes The allele combination in an individual A size-order display of chromosomes Genetics on Medicine & Dentistry Prof.. Genetics on Medicine & Dentistry 2013 Prof. carries genes An allele. ± account for 50% of childhood blindness deafness. Nov.· · A characteristic manifest in a hybrid (heterozygote) dominant A recessive characteristic ± expressed only in an individual with 2 copies of gene homozygous Mendel proposed: ± each individual has two genes for each characteristic · one is inherited from each parent & · one is transmitted to each child. 2013 ----------------------. a gene variant Chromosome not involved in sex determination Structure. Qureshi. learning difficulties & deaths. DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. 2013 ----------------------.. of DNA & protein. DUHS ----------------------. ± affect 5% of population by age 25 · Molecular genetics is at forefront of medical research · Human Genome Project & prospect of gene therapy represent major new initiatives that will revolutionize management & treatment of genetic diseases 8-30am 1st Sem 2013 6th Batch HBMS 701.Page 149----------------------- . Qureshi. with noticeable effect in one copy A sequence of DNA with known function All of the genes in a population A complete set of genetic instructions in a cell including DNA (encoding protein & other DNA) Study of how genes interact.Page 147----------------------· Genetic disorders are present in at-least ± 2% of all neonates. Nov.. Qureshi. Nov.

DUHS 8-30am 1st Sem 2013 6th Batch HBMS 701. complex trait A change in a gene that affects the individual's health . Qureshi.· · · · Term Mendelian trait Multifactorial trait Mutation Definition A trait completely determined by a single gene A trait that is determined by one or more genes & by environment. 2013 .. appearance or biochemistry A diagram used to follow inheritance of a trait in The observable expression of an allele combination A site in a genome that varies 1% or more of a population An allele that exerts a noticeable effect only Pedigree a family · Phenotype · Polymorphism · Recessive when · Sex chromosomes present in two copies A chromosome that carries genes whose presence or absence determines sex Genetics on Medicine & Dentistry Prof. Nov.

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