GEN 3020: Ch.


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Genetics through the Ages:  Principles of heredity were first demonstrated 10-12 thousand years ago (domestication)  Assyrians began artificial insemination  People knew to avoid spouses with undesirable traits  8,000BC: plant cultivation  5,000BC: Artistotle-vital heat (male) and physical substance (female) necessary to reproduce Ideas on human reproduction and heredity:  Inheritance of Acquired Characteristics o Hippocrates and Aristotle (and Lamarck, later) proposed traits acquired in life were incorporated into hereditary info and passed on Epigenesis: organism is derived from substance in egg that develop during embryonic development Robert Hooke – 1665 discovered cell using microscope Preformationism – inside egg/sperm is tiny adult (homunculus) o Vs. epigenesist Blending Inheritance – offspring are blend of parents

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Fixity of Species – (19th century) animals and plants appeared on planet and have not change since (Linnaeus was a proponent) Gregor Mendel:  1822-1884  Discovered basic principles of heredity  Crossed pea plants and analyzed patterns of transmission  Rumored that he wanted to study rats o Would have been much too complicated Charles Darwin: 1809-1892 Theory of evolution through natural selection Trip on Beagle – Origin of Species – heredity was the fundamental building block of evolution August Weismann:  Wanted to disprove Inheritance of Acquired Characteristics  Cut mice’s tails off (22 generations)   

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Purposed Germ-plasm theory – cells of reproductive system carry complete set of info Genetics: 1902-Sutton suggested chromosome were the home of genes 1953-Watson, Crick, and Franklin develop 3D structure of DNA 1966-chemical structure of DNA resolved 1970s-recombinant DNA technology 1977-Gilbert & Sanger developed DNA sequencing techniques 1983-PCR 1995-complete sequence of an organism

 2001-HGP nears completion Concepts in Genetics:  Eukaryote v. prokaryote  Genes are fundamental unit of heredity  Alleles-one of several forms of a gene (A v. a)  Phenotype v. genotype  Traits-not inherited, but reflect genotype and environment  DNA & RNA carry genetic info  Genes located on chromosomes  Evolution is genetic change

GEN 3020: Ch. 2
3 Main Groups of Life: 1. Eubacteria a. Eu- ―true‖ 2. Archaea (shares some traits with Eukaryotes) 3. Eukaryotes a. Pro- ―pre‖ b. Karyote- ―nucleus‖

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Microscope opened eyes to world of cell physiology  Zaccharias Janssen & Robert Hooke Chromatin winds DNA around histone proteins Viruses are NOT bacteria, cells, or eukaryotes  Cannot live without host  Most closely related to host when looking at genome sequence  Can only reproduce inside of host cell  Not alive, has to be inside something living to live Prokaryote Cell Reproduction:  Chromosome replicates, plasma membrane grows and chromosomes separate. Cell divides. Eukaryote Cell Reproduction:  Usually 2 sets of chromosomes from mother and father (homologous pairs)  2 sets of genetic info: diploid, 2n (most eukaryotic cells)  1 set of genetic info: haploid, n (ex: reproductive cells)

Homologous pairs: alike in structure/size. enters G1: cell growth (can enter G0. G2): cell growth  G1: 5 hours  S: 7 hours  G2: 3 hours o S: DNA synthesis o Cyclin levels change during cell cycle: rises during mitosis then drops o Increasing cyclin levels leads to G2 because of cyclin dependent kinase CDK) B-cell lymphoma can be cause my mutation in cyclin Overexpression of cyclin found in breast and esophageal cancer o Mitosis occurs in 1 hour  Prophase:  DNA is already replicated  Chromosomes condense  Mitotic spindle beings to for from centrosomes in animal cells    Nuclear envelope disappears  Microtubules contact chromatids Metaphase:  Chromosomes arrange in single plane (metaphase plate) Anaphase:  Sister chromatids move toward opposite poles (after separation: chromatids = chromosomes)    . when cells will not divide) o Beyond G1. carry genetic info for same characters o Humans have 23 homologous pairs (2 meters end to end)  X and Y chromosome are different in size but still match up Cell Cycle:  Uses lots of ATP  After cytokinesis. cell is committed to divide o Interphase (G1. S.

Acrocentric 4. Metacentric 2. which urged Darwin to publish his own book  phrenology: tool to assess human intelligence Meiosis v. Depolymerization of tubulin at + end (microtubules shorten) 2. Telocentric Chromosome Structure: Force to move chromosomes come from two sources: 1. Nocodazole causes Depolymerization of microtubules *Wallace: friend of Darwin.stabilizes microtubules 4. Telophase: 4 Major Types of Chromosomes: 1. Molecular motors 3. Submetacentric 3. Mitosis: . wrote to Darwin about his book. Taxol.

Mitosis Single nuclear division Results in the same # of chromosomes Yields genetically identical cells Meiosis Two cell divisions yields 4 cells (usually) Newly formed cell has ½ # of starting chromosomes Genetically variable cells (Crossing over & random distribution) Meiosis I:  Prophase: condensing chromosomes. # of possible combinations= 2^n (8 million in humans) . spindle begins to form o Crossing over occurs o Nuclear membrane breaks down Metaphase I: chromosomes align on metaphase plate Anaphase I: homologous pairs of chromosomes are separated o Interkinesis: egg development nuclear membrane reforms & DNA relaxes Telophase I: cytoplasm divides after chromosomes arrive at spindle poles II: same as mitosis    Meiosis Consequences of Meiosis:  Each cell usually produces 4 cells  Chromosome # is reduced ½  Cells produced are genetically distinct from parent cell o Crossing over o Random distribution  Without crossing over.

recessive traits. produces many offspring o Had genetically pure stocks of different types of peas to start studies o Avoided characters that exhibited variation (either/or characteristics) o Used experimental approach-hypothesis driven research & thorough records . the parents of affected individuals are likely to be related in some way  1902 discovered hereditary basis of alkaptonuria  First to apply basic principles of genetics to human disease-study how genes or a trait are passed from one individual to the next  Proposes hypothesis that the information for producing specific enzymes in humans is inherited Mendel:  1856-1863: breeding experiment  1900: work is recognized  Effectiveness was due to: o Choice of subjects-easy to grow. 3 12/6/2013 5:48:00 AM Archibald Garrod:  Noted that several children of the same family had alkaptonuriadarkening of urine due to oxidation of air in homogentistic acid  For rare.GEN 3020: Ch. grows rapidly.

Only GENOTYPE is inherited Mendel Concluded: a. which look like one parent. 1900s: Walter Sutton: studied insects  Homologous pairs of chromosomes consists of one maternal and one paternal  Developed Chromosome Theory of Heredity   . must have genetic factors from both (because of F2 results) b. Two alleles segregate into gametes. Two alleles separate when gametes are formed-one allele for each gamete Principle of Segregation: Mendel’s 1st law Each individual diploid organism possess two alleles for any particular characteristic. and this occurs randomly and in equal proportions. F1.

0879 Principle of Independent Assortment:  Mendel always got a 9:3:3:1 ratio in dihybrid crosses  Alleles at different loci separate independently of one another o Characters must be located on different chromosomes!!   .Homologous pairs segregate independently at meiosis: alleles segregate during anaphase I or II depending on whether crossing over occurred Mendel’s observations were the result of inheritance of slightly different DNAs (alleles)  Wrinkled gene-gene for starch branching enzyme  Insertion of TE (a mobile DNA) inactivates the gene in peas-if both alleles are inactivated Binomial Expansion & Probability:  (a+b)n Probability of having three kids of five with albinism? o A=probability of having child with albinism= ¼ o B=probability of having child without albinism= ¾ o (a+b)n= a5 + 5a4b + 10a3b2 +10a2b3+5ab4 + b5 o We are interested in 10a3b2 =10(1/4)3 (3/4)2 =0.

Waardenburg Syndrome:  Autosomal dominant trait  Deafness  Fair skin  White forelock  Visual problems .

Autosomal Dominant Traits:  Appears equally in males and females  Unaffected individuals to not transmit to offspring  Affected have at least one affected parents  Ex: familial hypercholesterolemia (elevated blood cholesterol) o Defect in ability to take cholesterol out of the blood o Not soluble. 2x higher than normal cholesterol o Homozygotes have big problems. Ex: Cystic Fibrosis: formation of cysts in the pancreas. listless and weak at 6 mths. may involve closely related individuals mating  Ex: Tay-Sachs-normal at birth. prone to early heart attack Autosomal Recessive Traits:  Appears equally in males and females  Skip generations.  neurological problems with death around 2-3yrs. so is transported with proteins and phospholipids o LDL: low density lipoprotein-attaches to LDL receptor (defect is in receptor) o Hets-deficient in receptor. No functional LDL receptor6x higher cholesterol.. leads to mucus and infection in lungs o 1/22 white Americans are Hets for CF o Most common non-sex linked traits in white America o CF Gene (Chromo 7)-CFTR CF transmembrane conductance regulator . leading to pancreas degenerating into fibrous structure.

disease will occur) Heterozygous females pass the trait to ½ of sons and daughters Dominant Traits: Do not skip generations Affected males pass to all daughters. none of sons Heterozygous females pass the traits to ½ of sons and daughters Ex: hypophosphatemia-bone deformations like rickets-defective transport of phosphate . Ex: Sickle cell anemia: o 1/12 black Americans are Hets o Allele is more resistant to malaria: sickle cell is more common in malaria infested areas X-linked Recessive Traits:    X-linked     Affected males cannot pass to sons. but can pass to daughters (as carrier) o Affected males pass to all daughters. so if it is mutated. none to sons Unaffected daughters can pass to sons (appears more frequently in males (because they only get one X chromosome.

or X-linked trait (because of multiple alleles)  Multiple genes involved that results in this What if a traits has a single pattern of inheritance yet is caused by a mutation in a number of genes? o Porphyria: metabolic disorder leading to abnormal behavior (heme biosynthesis problem. easily stretched skin  Autosomal dominant. Females are not affected as much because heterozygous females have good X chromosome to make up for bad one Y-linked traits only appear in males  Complications:  Family history is not always available  What if a genetic disorder has more than one pattern of inheritance? o Ehlers-Danlos: loose joints. autosomal recessive. King George III)  .

 Autosomal dominant traits caused by mutations on Chromo 1. 11. 9. and 14 .

but 40 express phenotype.  Husband reports decline in memory. 4 12/6/2013 5:48:00 AM Case Study:  Woman presents to ER complaining of uncontrollable jerking movements progressing over 3 mths. increased irritability  Father suffered similar symptoms  MRI reveals atrophy of the caudate nucleus with dilation of lateral and third ventricles 1872: Dr. George Huntington-described disease that hits middle age  Initially.% of individuals having a particular genotype that express the phenotype o Ex: 50 people have allele for polydactyly.GEN 3020: Ch. requires modification of Mendel’s principles (or more severe disease manifestation in each generation Penetrance & Expressivity:  Incomplete penetrance-genotype does not yield phenotype o Ex: polydactyly  Penetrance. mild neurological problems-impaired motor function/insanity & death     No cure Huntington’s Disease Autosomal dominant trait Gusella lab mapped genes for HD o Disease due to expansions/contraction of unstable region of DNA o Expansion of repeats=disease (rapid expansion=juvenile to which a character is expressed Due to: o Effects of other genes o Environmental factors Presence of a gene does not guarantee its expression!  . 40/50=80% penetrance   Expressivity. usually from father to offspring) o Anticipation-earlier appearance of a trait as it is passed on.

Incomplete Dominance:  Dominance is related to the phenotype of the heterozygote  1:2:1 ratio is incomplete dominance Codominance:  Phenotype of the heterozygote includes the phenotypes of both  homozygotes Ex: Sickle cell .

get a 2:1 ratio-segregation of lethal allele (usually recessive)  In mice. allele is recessive for death (requires homozygosity) while it is a dominant effect on color  Mutation cause ―pleiotropic effects‖-impacts several aspects of a  Multiple     phenotype Dominant lethal: will not see it. HbA allele is dominant in regards to presence/absence of anemia Lethal Alleles:  Expect a Yy x Yy cross to yield a 1:2:1 ratio  Instead. unless late onset (like Huntington’s) Alleles: M = mallard pattern MR = Restricted md = dusky MR>M>md = allelic series o MRMR = restricted o MRM = restricted o MRmd = Restricted o MM = Mallard o Mmd = mallard o mdmd = dusky # of genotypes possible=[n(n+1)]/2 o n= # of different alleles at a locus Blood types:   .

Red color r . allows chlorophyll to remain.dominant.recessive allele. no color C .recessive.dominant.Gene Interactions:  Ex: genes at two loci interact to produce single characteristic     R . . decomposition of chlorophyll (green pigment) c .

e does not (yellow)  B_E_ .brown 3  B_ee – yellow 3 (4/16 yellow)  Bbee – yellow 1  Allele e is epistatic to B and b Dominant epistasis:  . b=brown  E allows dark (black or brown).Epistasis: the effect of one gene hides the effect of another  Similar to 9  bbE_ . except dominance involves masking of genes at same locus  Look for epistasis when ratio is odd  Recessive epistasis: o Lab coat color:  Pigment B=black.

B.are the mutations all in the same gene or in three different genes? o Solution: cross homozygous recessive mutants and see if progeny have the wt phenotype! .o W_Y_ .white o W_yy . get three true breeding white plants (A. and C) o So.yellow o wwyy – green Complementation: determining if mutations are in the same or different loci  Ex: harebell plants blue o Mutagenize. recessive allele of a single gene leads to mutant .white o wwY_ .


but expressed differently in males and females  Bb – bearded. usually leading to mild phenotype o Male sex hormones likely influence expression of baldness allele Sex Limited Characteristics:  Determined by autosomal genes but only expressed in one gender  Ex: cock feathering is autosomal recessive o HH-males are hen feathered o Hh-males are hen feathered o hh-males are cock feathering Cytoplasmic Inheritance:   Mendel principles of segregation and independent assortment-genes are on chromosomes in nuclei Genes in cytoplasm: o Mitochondria (~37 genes. all mutated (white).Sex-Influenced Characteristics:  Determined by autosomal genes.000 bp. females require two o Allele is expressed weakly in females. and a mix of chloroplasts (variegated) Genes & the Environment: . circular genome. 15. but most cytoplasmic genes come from mother Egg is huge. dominant in males and recessive in females  Pattern-baldness is a sex-influence trait o Autosomal trait-can be inherited from either parent o Men require only a single bald allele. not dad  4 o’clock plants: variegated leaves-variegation caused by mutation in gene is needed to make green pigment (encoded in chloroplast)  Flowers: random segregation of chloroplasts from variegated branch yields eggs with all normal chloroplasts (green). sperm is small and all mitochondria are in tail region   (not part of fusion with egg)  Therefore most of mitochondria comes from mom. 2-10 copies/mito) o Chloroplasts Zygote-inherits nuclear genes from both parents.

feet.    Temperature-sensitive alleles (rabbits that turn black) Phenocopy-when phenotype caused by environment=phenotype cause by genotype Polygenic traits (polygeny)-many different genes are involved in how a characteristic results (many loci) o Different possible genotypes = 3n. laughter. males and females do not contribute the same DNA  Genomic Imprinting: occurs with autosomal genes-males and females contribute equal number of genes. short stature. where n is the number of loci with two alleles that influence trait Pleiotropy-one gene affects multiple character o Ex: PKU-person with single homozygous recessive allele phenotype=ID. We carry two copies of each gene 2. only one copy is expressed – but not always  Genes are somehow ―marked‖ during gamete formation or early in development  Prader-Willi syndrome/Angelman syndrome o Disease depends on whether syndrome is from mom or dad o PWS: small hands. frequently become obese due to insatiable hunger  Inherited from FATHER  Caused by absence of segment 11-13 on long arm of paternally derived chromosome o Angelman: large mouths. Sometimes. F x M) (not true)  X-linked genes. cytoplasmic genes. ID  Inherited from MOTHER . but expression is affected by parental origin o Genes from mom and dad are not equal-don’t contribute equally to offspring’s genotype 1. and light skin Genomic Imprinting:  Mendel: reciprocal crosses give identical results (M x F. ID. puppet-like movements. blue eyes.

undeleted paternal chromosome Epigenetics:  Factors that exist on top of genes  Rats under stress experiment o Modification in DNA that led to gene expression  Turning genes on or off depending on whether environmental stimuli is experienced END OF EXAM 1 . Maternal segment of ch15 is deleted.

Completely linked (on same chromosome. close together so crossing over is rare) 3. Morgan (who suggested that genes on the same chromosome segregated together and that those closely linked were rarely subject to recomb) o 1911-generated first map of chromosome based on recombination frequency o Review: Principle of segregation. & Gene Mapping:  Alfred Henry Sturtevant-student of T. but some distance apart. Incomplete linkage (genes on same chromosome. On different chromosome (independent assortment.GEN 3020: Ch. & Crossing Over  Genes may be: 1. combine randomly) 2. arises from independent assortment in Anaphase I of meiosis  . 5 12/6/2013 5:48:00 AM Linkage. Recombination. Linkage. Principle of Independent Assortment.H. progeny/total # progeny *100% Coupling & Repulsion:  Coupling (cis)-wild type alleles on one chromosome/mutant on the other  Repulsions (trans)-each chromosome has one wild type and one mutant allele Independent Assortment. Chromosome Theory of Heredity  Linked genes-those that are close together on same chromosome travel together during meiosis and do not usually sort independently o Travel together unless crossing over occurs in Meiosis I o More likely to cross over if farther apart Crossing Over:  More likely the farther apart two genes are on a chromosome  Does not have to occur  Nonrecombinant progeny (MD or md) is much more frequent than recombinant progeny (Md or mD)  Recombination frequency: o # of recomb. allows some recombination) Interchromosomal Recombination-between genes on different chromosome.

use recombination frequencies to make chromosome maps  Distances are in terms of Map units (= 1% recombination frequency). aka centimorgans (cM) o Cannot measure recombination frequencies >50% Physical Maps . 50% is the frequency of recombination for genes on different chromosomes-so.Intrachromosomal Recombination-between genes on same chromosome due to crossing over in Prophase I of meiosis Testing for Independent Assortment:  Linkage between two genes requires several chi-square tests o Test for segregation at individual loci o Then test for independent assortment Genetic maps . Recombination frequency cannot exceed 50% for two genes 2. Genes that are far apart can undergo DOUBLE crossovers a.chromosome maps based on physical distances (base pairs) Gene Mapping with Recombinant Frequencies: 1. Appears that the crossover never occurred  Double crossover yields recombinant chromosomes with altered middle genes  . impossible to discern between two genes that are far apart on the same chromosome. an those on different chromosomes 3.


  Identify nonrecombinant progeny: most numerous Identify double crossovers: least numerous b/c low probability of double event  Compare nonrecombinant parent to most similar double crossover o Compare other nonrecombinant parents to other double crossover  Difference between two must be in the middle Calculating Recombination Frequency (or Map Distances)  Draw lines where you know there has been a crossover .

progeny will all be wild type Somatic Cell Hybridization:   Must be on chromosome 4 Molecular Markers and Mapping:  Marker-site of Heterozygosity that does not yield measurable phenotypic change o SNP-single nucleotide polymorphism o RFLP-restriction fragment length polymorphism . ½ the progeny will have mutant phenotype  If not. then divide by total number of progeny x100  Probability of double crossover occurring can be calculated based on probability of the two single crossovers multiplied together  Interference can occur-one even can influence another (do not always get expected results) Interference and Coefficient of Coincidence  COC= # of observed double crossovers/# of expected double crossovers  Interference= 1-COC Deletion Mapping:  Cross an individual that is homozygous for a recessive mutation with an individual that is heterozygous for a deletion in a chromosome  If the gene is in the deleted part of the chromosome.Add up all recombinant progeny with difference at that gene.


fewer than %1 of cholera patients die ***** Bacterial Transformation:  DNA taken up from surrounding and incorporated in genome  Can occur naturally (DNA from dead cells in environment)  Competent-cells that can take up DNA  Do this by electroporation Gene Mapping using Transformation:  Rate of cotransformation is inversely proportional to distances  Viruses:  All organisms are infected by viruses  Nucleic acid coated in protein  dsDNA. had pump handle removed. ssRNA.GEN 3020: Ch. plotted cases around a single well. 1854: Soho epidemic of London o Outbreak of cholera  Dr. dsRNA  Linear or circular genomes Bacteriophage: Two Alternative Life Cycles between genes Closer genes go together more easily . 6 12/6/2013 5:48:00 AM Bacterial and Viral Genetic Systems:  August 31. ssDNA. John Snow-thought cholera was spread through water. solved problem  Cholera epidemic has lasted more than 20 years in Africa  With prompt rehydration.

   Can alternate back and forth Virulent phage reproduce only through lytic cycle Temperate phage use either lytic or lysogenic cycle Alfred Hershey & Raquel Rotman:  Studied phage recombination  Different types of phage could undergo recombination and produce different phenotype/genotype  Were able to find recombination frequency for h+r+/h-rLederberg & Zinder:  Studied bacteria of different genotypes  Mix two different auxotrophic strains Transducing Phage: .

taking host bacterial DNA with it  Can be unstable when infecting new bacteria Mapping Bacterial Genes:    Interrupted conjugation Transformation Transduction  .Requirements: o Phage must degrade bacterial chromosome o Packaging DNA into phage cannot be specific for phage DNA o Recombination must occur with the recipient chromosome  Only a small portion of the bacterial DNA can be transduced! Specialized Transduction:  Occurs when prophage imperfectly excises.

female grasshoppers had 1 more chromosome than males o Stevens & Wilson (1905): female grasshopper have 2 X chromosomes. has either male or female reproductive systems Mechanisms: o Chromosomal sex-determining system o Genetic sex-determining system o Environmental sex-determining system Chromosome theory of inheritance: genes are located on chromosome and chromosomes are substrate for gene segregation History: o Henking (1891): Male insects had a strange ―body‖ in nuclei=X body o McClung: X body=chromosome. also smaller X in male cells called Y  X & Y separate into different sperm cells. half sperm receive X. other half get no sex chromosome o Heterogametic sex-sex that produces two different gametes      . femals have two XX. 7 12/6/2013 5:48:00 AM Darwin:  Noted hairless. reptiles. XO-simple system.GEN 3020: Ch. has both female and male reproductive   structures Dioecious: ―two house‖. XY works in some plants. males have single X (O=no chromosome) o At meiosis. weird teeth quality in men  Fathers did not pass to sons. and ALL mammals XX. but unaffected daughters could pass to sons  Mostly occurred in men Sex Determination:  Sexual reproduction: formation of offspring that are genetically distinct from parent  Sex (noun): defined by phenotype of individual (not phenotype)  Monoecious: ―one house‖. while egg cells all get single X Size and genetic content of X & Y are different (pseudoautosomal regions allow the two to find each other during meiosis) XX. insects.

o Homogametic sex-sex that produces identical gametes  ZZ. the other half with W o Found in birds. ZW-male is homogametic. some amphibians Haploploidy & Social Insects:  Some members have no sex chromosomes: males develop from unfertilized egg  Not XO system! Genetic Sex-determining System:  No obvious difference in chromosomes  Genes determine sex of individual  Similar to chromosomal sex-determining system Environmental Sex-determining System:  Ex: common slipper limpet: sequential hermaphroditism (change sex as they go to bottom of pile)  Ex: alligator: warm temperatures produce male. cool temperatures produce females Sex Determination in Drosophila:      Females XX. moths. female is heterogametic o Female produces two different gametes. ratio of autosomes to X determines sex (=genic balance system) X has genes for female-producing effects. males XY-but Y does not determine maleness Instead. 3 had white eyes-Morgan attributed mutation  Bridges hypothesized that X chromosome fails to separate in anaphase I of meiosis X-Linked Color Blindness in Humans:  Red-green color blindness is due to lack of green and red absorbing pigments in the cone cells of the eye  Locus for these pigments are close together on the X chromosome . half with Z chromosome. autosome have genes for male-producing effects Sex determined by X:A ratio X-linked white eyes in drosophila: o Thomas Hunt Morgan-first explained sex-linked inheritancefound some traits were associated with one sex or the other Nondisjunction:  1237 flies in F1.

but mentally deficient-severity increases with increase in X chromosomes Role of Sex Chromosomes:  X contains genetic info for both sexes-at least one X is required  Male-determining gene is located on Y  Females need at least two Xs to be fertile  Additional X chromosomes are detrimental Y Chromosome in Producing Male Phenotype:  All humans have neutral gonads early in development.)  Small testes. If testes develop. XXYYY. reduced pubic/facial hair)  Usually sterile Poly-X Females:  XXX. XXXX females  Tall thin. breast enlargement. which triggers male character development and Mullerian-inhibiting substance. etc. usually fertile  Normal female anatomy. which degrades female reproductive tracts  SRY (Sex-determining region Y) was discovered in 1990 o Found in all XX males Androgen-insensitivity Syndrome:  Other genes besides SRY can influence sexual development  Persons with androgen-insensitivity syndrome have female sexual characteristics. XXY chromosome (could be XXXY. oviducts or ovaries  Testes found in the abdominal cavity  Genes for male and female secondary characters on autosomescontrol of expression is key Dosage Compensation: . they secrete testosterone.Turner’s Syndrome:  Females with XO chromosome  Immature secondary sex characteristics. but no uterus. low hairline and folds of skin on neck  Usually sterile  No known cases of no X at all  Result of disjunction from mom or dad Klinefelter’s:  Male.

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Because females have two copies of every X-linked gene, they should produce twice the amount of gene products as males Overcome by dosage compensation-fruit flies double the activity of genes on X in males Barr (1949)-observed darkly staining body in nuclei of cat cell=Barr body Lyon (1961)-proposed that Barr body was inactive X chromosome=Lyon hypothesis X inactivation-females can turn off genes in different X chromosomes o Takes place early in development o Inactive X remains inactive (as do all somatic descendent cells) o X inactive-specific transcript (XIST) gene-located on the X chromosome-is required

Aneuploidy:  Changes in # of individual chromosomes  Three reasons: 1. Loss of chromosome which has lost its centromere 2. Robertsonian translocation 3. Nondisjunction Types: o Mullisomy: loss of both members of homologous pairs: 2n-2 (n=haploid # of chromosomes – humans 2n=46) o Monosomy: loss of a single chromosome: 2n-1 o Trisomy: gain of a single chromosome: 2n+1 o Tetrasomy: gain of two homologous chromosomes: 2n+2

GEN 3020: Ch. 8

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Bad Deletions:  Deletion of centromere (no regulation on mitosis and meiosis); loss of essential genes: lethal if homozygous for loss  Heterozygous deletions: o Gene product will be unbalanced o Allows recessive alleles or undetected chromosome to e expressed (pseudodominance) o Some genes present in two copies to produce enough gene product (haploinsufficient) Paracentric Inversion:  Inversions that do not include the centromere  Crossing over occurs and connects chromosomes Pericentric Inversion:  Inversion does include the centromere (changes arm lengths)  Connected chromosomes Translocation:  NOT crossing over!  Between homologous chromosomes  Nonreciprocal (n=move one way, from one chromosome to another  in an unequal exchange Result in: o Altered gene expression due to position o Gene breakage may occur Ex: Robertsonian Translocation: causes some forms of Down Syndrome o End with gametes that are nonfunctional and some that are functional The only major structural differences:

o # of ******* inversions  Recent fusion of 2 chromosomes to form human chromosome  Reciprocal translocation between gorilla chromosome which responds to human chromosomes 5 & 17 Fragile X-Syndrome: chromosome looks compressed  Affects a lot of males  Most common form of inherited mental impairment  Results in # of trinucleotide repeats & permutation

 Leads to methylation & blockage of transcription Different Types of Chromosome Mutations:  3 types of rearrangements associated with cancer o Deletions: loss of tumor suppressor genes o Inversions: break in genes or fusion to yield new genes o Translocations  Chronic Myelugenous Leukemia  Moves cancer causing things to position  Burkih’s Lymphoma: C-myc is relocalized, under control of improper regulatory DNAs- C-myc expressed in Bcells

9 12/6/2013 5:48:00 AM Do wolves and coyotes mate in wild?  Study mitoDNA o Comes from mom (uniparental inheritance) o Evolves rapidly  Wolves had coyote-like mito…female coyotes must have mated with male wolves  Cytoplasmic inheritance: uniparental  Petite mutation in yeast  Mitochondrial genes are critical to life: mess up in mitochondria=ATP production problems Mt defect in humans: o MERRF myoclonic epilepsy and dragged red fiber disease o ATAXIA. mtDNA/cpDNA has many similarities to eubacterial DNA Ribosomes are similar to eubacteria Antiblotea that block pathways in eubacteria inhibit same paths in mt/cp  . 4. muscle weakness: all exhibit cytoplasm inheritance  Cells that have more than one type of DNA in cytoplasm=heteroplasmy o Seventy of a defect in this DNA is often determined by proportion of mutant DNA Endosymbiotic Theory: 1.GEN 3020: Ch. 3. Many eukaryotes are hurt to endosymbiotic bacteria 2.

out of ~16.7% identical to modern human DNA 98.000 2008: complete mtDNA sequence from 38.000 year-old Neanderthal fossil from Croatia o Allows divergence estimate 2010: Max Planck Institute-draft genome (60%) sequence of a Neanderthal 99.8% identical to chimpanzee DNA 1-4% of DNA comes from Neanderthal DNA (outside of Africa)     .Neanderthals:   1997: Neanderthal DNA successfully extracted from mtDNA 397 bp.

contained slightly acidic material-named ―nuclein‖ Kossel: determined bases (A. 2003. C. phosphate. 100 lbs Infected with whipworm. have smooth coat  R=rough.use isotopes to locate birth place (less than 60km away)  Forensic analysis: not a fake Genetics Material: Early known properties  Must encode complex information  Must be capable of being replicated faithfully  Must contain enough information to yield phenotype Genetic Timetable:    1869: Miescher: studied pus. 5’2‖. pollen in gut suggested death in late spring/summer Rib broken after death. 1991: found in the mountains b/t Austria and Italy 5.GEN 3020: Ch. 10 Iceman:           12/6/2013 5:48:00 AM Sept.300 years old In his 40s. MacLeod. 31. destroy DNA: mice live . T. and McCarty  Isolated transforming principle  Destroy protein: mice die. & G) Levene: nucleotide (most basic component of DNA) = sugar. eventually found stone arrowhead in shoulder DNA more like modern Europeans. and base o Proposed tetranucelotide theory-DNA is made up of units of four bases in fixed sequence-DNA too regular to encode info (protein is genetic material) Chargaff’s Rule: A=T and G=C  Fred Griffith (1928) Transforming Principle:  Used streptococcus pneumonia  Virulent strain has polysaccharide coat. less like South Americans Oct. avirulent  Some S could become R spontaneously Avery. fleas Pollen suggested late autumn death Fractured ribs suggested injury (accident/fight) Revisited. isolated nuclei.

broader Probably does not exist in nature Left-handed helix Zigzag backbone  Sites of active DNA can make Z-DNA Central Dogma of DNA:  DNA replication  transcription  RNA?  Not always true Fatal Familial Insomnia:  Usually begins between ages of 40-60  Usually runs in families  Initially have minor difficulties sleeping.Nobel Prize (1962) for DNA structure-explains Chargaff’s Rule: A=T  G-C pairs are more stable (3 bonds instead of two) than A-T pairs RNA:  Usually single stranded  U instead of T  Chargaff’s Rule does not apply B-DNA:  Exists in presence of water  Most common DNA in humans  Most stable under physiological conditions   A Form:    Z-DNA:   Alpha helix (right-handed/clockwise) 10 bp per rotation Alpha helix Shorter. then lose ability to sleep altogether  Eventually die Transposable Elements:  Repetitive and possible mobile DNAs  Present in all organisms  50% of human genome  Can cause mutations by inserting into genes or causing rearrangements  Common features: .

     o Flanking direct repeats-not pair of element Lack genes required for autonomous replication SINEs-short interspersed sequences Why so common? o Cellular Function Hypothesis: TE serve a function in cell o Genetic Variation Hypothesis: some variation is good! (evolution) o Selfish DNA hypothesis: TE serves no purpose-exists to spread Ex: neurofibromatosis: mutation of TE Mutagenic: insert into genes or disrupt gene function .

11 12/6/2013 5:48:00 AM Because synthesis of both strands takes place simultaneously. two units of DNA polymerase III must be present at the replication fork-one for each strand  Ligase comes in to replace DNA polymerase I DNA polymerase I: single polypeptide DNA polymerase III: holoenzyme. a complex enzyme made up of multiple subunits Each Active Replication Fork Requires 5 Basic Components:  Helicase to unwind DNA  Single-strand-binding proteins to keep the nucleotide strands separate long enough to allow replication  The topoisomerase gyrase to remove strain ahead of the replication fork .GEN 3020: Ch.

Primase to synthesize primers with a 3’-OH group at the beginning of each DNA fragment  DNA polymerase to synthesize the leading and lagging nucleotide strands Basic Rules of Replication  Replication is always semiconservative. New nucleotide strands are made complementary and antiparallel to their template strands. and     repair mechanisms. Replication is continuous on the leading strand and discontinuous on the lagging strand. proofreading. Tus blocks the movement of helicase. and mismatch repair The sequential application of multiple mechanisms ensures highly accurate DNA replication Eukaryotic DNA Replication:  Multiple origins of replications per chromosome (the originrecognitions ORC)  Replication licensing factor  Several different DNA polymerases have different functions  Immediately after DNA replication. thanks to precise nucleotide selection. Replication takes place at very high rates and is astonishingly accurate. Coli binds to these sequences. thus stalling the replication fork and preventing further DNA replication Fidelity of DNA Replication:  Processes of nucleotide selection.  DNA synthesis is initiated by short segments of RNA called primers. two phosphates are cleaved from a dNTP and the resulting nucleotide is added to the 3′-OH group of the growing nucleotide strand.  The elongation of DNA strands is always in the 5′→3′ direction. nucleosomes are assembled  . proofreading.  Replication begins at sequences called origins. in the polymerization of DNA. Termination:  Two replication forks meet  Tus in E.  New DNA is synthesized from dNTPs.

In absence of special mechanisms. DNA replication would leave gaps due to the removal of primers at the ends of chromosome (telomerase is responsible for replication of chromosome ends) Molecular basis of Recombination:  Holliday Model  *********** READ OUT OF BOOK****************  .

12 *In notebook* 12/6/2013 5:48:00 AM .GEN 3020: Ch.

consisting of the proteins necessary to catalyze the synthesis of RNA Transcription Unit: normally contains a promoter. 13 12/6/2013 5:48:00 AM Transcription:  One strand of DNA is used for template for creation of DNA  Enzyme RNA polymerase reads nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule that looks like the coding strand  Each gene is transcribed from a single strand. Raw materials (substrates) needed to build a new RNA molecule iii. and a terminator  . an RNA-coding sequence. A DNA template ii. but different genes may be transcribed from different strands  Requires 3 major components: i. Transcription apparatus.GEN 3020: Ch.

ending the transcript Number on sequence if negative is downstream and refers to the location in relation to the transcription start site (downstream is positive) Two major types of bacterial terminators: o Rho-dependent o Rho-independent  Terminator contains inverted repeats followed by string of approx.  Promoter: o Serves as sequence to which transcription apparatus binds o Determines the first nucleotide that is transcribed into RNA and the direction of transcription o Determines which DNA strand is the template Occurs in 3 steps: o Initiation: control of transcription is regulated by transcription factors o Elongation: RNA polymerase adds nucleotides to growing RNA o Termination: sequences in the DNA prompt the RNA polymerase to fall off. six adenine nucleotides   .


How transcription is initiated in bacteria: .

RNA is transcribed from single-stranded DNA. 5. only certain parts of the DNA are transcribed. Transcription is always in the 5′→3′ direction. and ends transcription after a terminator has been transcribed. Transcription is a selective process. Ribonucleoside triphosphates are used as the substrates in RNA synthesis. Normally. and the resulting nucleotide is joined to the 3′-OH group of the growing RNA strand. meaning that the RNA molecule grows at the 3′ end. . 3. 4. multimeric enzyme. 8. A sigma factor enables the core enzyme of RNA polymerase to bind to a promoter and initiate transcription. Promoters contain short sequences crucial in the binding of RNA polymerase to DNA. and other subunits that may join transiently to perform additional functions. 7. only one of the two DNA strands—the template strand—is copied into RNA. Two phosphates are cleaved from a ribonucleoside triphosphate. Transcription depends on RNA polymerase—a complex. 6. RNA polymerase consists of a core enzyme. these consensus sequences are interspersed with nucleotides that play no known role in transcription. begins transcribing at the start site of the gene. 2. RNA polymerase binds to DNA at a promoter. RNA molecules are antiparallel and complementary to the DNA template strand.Basic Rules of Transcription 1. which is capable of synthesizing RNA.

GEN 3020: Ch. 14 *In notebook* 12/6/2013 5:48:00 AM .

produces an apurinic site o Deamination: loss of an amino group (NH2) from a base   Can be induced by mutagenic chemicals Planned mutations (external factors) o Result from influence of extraneous factor. germ-line mutation) o Causes  Chromosome mutation: number or structure of one or more chromosomes is mutated (aneuploids. or hydrogen peroxide Point mutation: change of one letter (substitution) o Base substitutions:  Transitions:  Purine  purine (AG. polyploids)  Autosomal mutations: occur within genes located on the autosomes  X-linked and Y-linked mutations occur within genes located on the X and Y chromosome  Spontaneous mutations (internal factors) o Happen randomly o Low rate o Arise from altered base structures and from wobble base pairing  Wobble base pairing: T/G and C/A: result of the flexibility in DNA structure) o Depurination: loss of a purine base from the nucleotide. TA/G)  . GA)  Pyrimidine  pyrimidine (CT.GEN 3020: Ch. X-ray. 15 12/6/2013 5:48:00 AM Mutations: essential to study of genetics and useful in many biological fields  Can be classified in various ways: o Location (somatic mutation. either natural or artificial o Mutagen: any environmental agent that significantly increases the rate of mutation above the spontaneous rate o Chemically induced: radiation-UV. radioactive isotope  Causes oxidative damage from superoxides. hydroxyl radicals. TC)  Transversions:  Purine  pyrimidine (AC/T. GC/T)  Pyrimidine  purine (CA/G.

but more common in repeat sequences o Unequal crossing over: produces insertions/deletions Mutations can be classified according to their phenotypic effects as o Loss-of-function mutations o Gain-of-function mutations o Visible (morphological) mutations o Nutritional (biochemical) mutations o Behavioral mutations o Regulatory mutations  . Deletion/Insertion: o Frameshift mutation: alters the reading frame of a gene o In-frame insertion: insertion of some multiple of three nucleotides which does not alter the reading frame of the gene o Expanding trinucleotide repeat: mutation in which the number of copies of a trinucleotide (or some multiple of three nucleotides) increases in succeeding generations. o May result from small slippage  Can occur anywhere in DNA.

leucine zipper Operon:  Eukaryotic genes are dispersed and typically each is transcribed into a separate mRNA  Many bacterial genes that have related functions are clustered and are under the control of a single promoter  These genes are often transcribed together into a single mRNA  . stresses. turning genes on and off in response to environmental changes   In multicellular eukaryotic organisms. zinc fingers. development) o Cell must be able to sense the stimuli  In bacteria. o regulatory gene: DNA sequence that encodes a protein or RNA molecule that interacts with DNA sequences and affects their transcription or translation or both. Control transcription of the structural genes o regulatory element: DNA sequence that affects the transcription of other DNA sequences to which it is physically linked. not transcribed o constitutive gene: is not regulated and is expressed continually.GEN 3020: Ch. gene regulation brings about cellular differentiation Terminology: o Genes: DNA sequences that are transcribed into RNA o structural gene: DNA sequence that encodes a protein that functions in metabolism or biosynthesis or that plays a structural role in the cell. Encode proteins. only a fraction of the genome is expressed (constitutive gene)  Can alter not only in the genes being turned on or off. gene regulation maintains internal flexibility. but also in the levels that the genes are expressed  Regulation gives organisms ability to cope with change in environment (nutrient availability. Regulatory proteins: DNA-binding proteins o Form hydrogen bonds with DNA bases o Forms: helix-turn-helix. 16 12/6/2013 5:48:00 AM Regulation:  At any one time.

but some are repressible (transcription is normally on and must be turned off)   Promoter operates whole system?? o Determines where transcription takes place Operator often determines when transcription takes place (activators or repressors) .  Operon: a group of bacterial structural genes that are transcribed together (along with their promoter and additional sequences that control transcription) Some operons are inducible: transcription is normally off and must be turned on.

coli  Lactose is one of main carbs in milk   3 genes in lac operon: b-galactocydase (Z). which increases efficiency of polymerase binding When glucose is high. and transacetylase (A) To utilize lactose as energy source. a reaction catalyzed by the enzyme Bgalactosidase Negative inducible operon Lacl: repressor Control & Catabolite Repression: Glucose enters glycolysis without further modification and therefore requires less energy to metabolize When glucose is low. cAMP (cyclic monophosphate) binds to CAP. transcription occurs Positive inducible: inactive activator does not bind. coli must break in into glucose and galactose. permease (Y). there is less cAMP to bind to CAP. no transcription Positive repressible: activator binds.Negative inducible: repressor binds to operator and prevents transcription Negative repressible: inactive repressor does not bind. E. so RNA polymerase cannot bind to DNA as efficiently and there is a low transcription rate Catabolite activator protein (CAP) exerts positive control over lac operon   Positive     . transcription occurs lac Operon of E.

so transcription occurs o When tryptophan is high.  Tryptophan operon: negative repressible operon o When tryptophan is low. the trp repressor is inactive. the repressor binds to the operator and prevents transcription Riboswitch: regulatory sequence in a RNA molecule o Molecules can bind and affect gene expression by influencing the formation of secondary structures in the mRNA o Can function as ribozyme: RNA molecule that can act as a biological catalyst Attenuation: type of regulation that can turn off transcription (using riboswitch)  . tryptophan binds to the repressor and activates it.

17 * READ BOOK* 12/6/2013 5:48:00 AM Eukaryotic Gene Regulation: Many features of gene regulation are common: DNA-binding protein The acetylation of histone proteins alter chromatin structure and permits some transcription factors to bind to DNA DNA Methylation: most common on cytosine bases adjacent to guanine nucleotides on the same strand (CpG) DNA regions with many CpG sequences are called CpG islands and are commonly found near transcription start sites Methylated: no transcription methyl groups are removed: initiation of transcription. such as on the inactivated X chromosome of female mammals .GEN 3020: CH. CpG methylation is also associated with long-term gene repression.

18 12/6/2013 5:48:00 AM .GEN 3020: Ch.

cells are unable to respond normally to cell-cycle checkpoints or are unable to undergo apoptosis if DNA damage is extensive  Leads to more mutations and development of cancer 2. etc. Regulation of cell-cycle progress is mediated by cyclins and cyclindependent kinases (CDKs) that regulate synthesis and destruction of cyclin proteins  . apoptosis. fewer somatic mutations are necessary for cancer to develop. and the person may have a predisposition to cancer  Mutations in different types of genes contribute to cancer: o Oncogenes 1. if not all. 19 12/6/2013 5:48:00 AM Cancer is a group of diseases characterized by cell proliferation  Uncontrolled growth  Most cancers are not inherited  Affects fundamental aspects of cellular function including DNA repairs. Hong Kong. Proto-oncogenes: genes whose products promote cell growth and division  Encode transcription factors that stimulate expression of other genes  Encode signal transduction molecules that stimulate cell division  Encode cell-cycle regulators that move through cell cycle Tumor-suppressor genes o Products normally regulate cell-cycle checkpoints and initiate the process of apoptosis o When they are mutated or inactivated.GEN 3020: Ch. cell-cycle.  Most. cancers arise from defects in DNA  Mutations in several genes are usually required to produce cancer  If one of these mutations is inherited. regulation. and signal transduction  Role of environmental factors in cancer: USA has higher rates of many different kinds of cancer than India.

Genes that regulate telomerase 6. Many tumor cells exhibit widespread reduction in the expression of many miRNAs . the tumor is malignant c. DNA-Repair genes 5. where they establish secondary tumors. Defects in signal transduction pathways:  An external signal triggers a cascade of intracellular reactions that ultimately produce a specific response  Cell growth and division is regulated by external signals  Both stimulatory and inhibitory signals. Genes that promote vascularization and spread of tumors a. and its growth and division are regulated by a delicate balance between these opposing forces. Cells that travel to other sites of body. 4. have undergone metastasis d.3. If cells remain localized. If cells invade other tissues. the tumor is benign b.

there would be more than 2 billion possible genotypes to examine (420) The digested DNA is separated by gel electrophoresis and subjected to Southern blot analysis DNA is transferred from the gel to a membrane. After exposing the membrane to X-ray film. but the repeated motif is shorter  Although hundreds of STR loci are present in the human genome.000 cells or 50 micrograms of DNA)  DNA should be relatively intact Autosomal STR DNA Profiling:  Small samples of DNA are amplified using PCR. the pattern of bands is measured. the FBI and other law enforcement agencies have selected 13 STR loci to be used as a core for forensic analysis Y Chromosome STR Profiling  . Scientists analyze about five or six loci to create a DNA profile Each person's profile will be unique because of the large number of possible VNTRs and alleles  A significant limitation of VNTR profiling is that it requires a large sample of DNA (10.GEN 3020: Special Topics Forensics: 12/6/2013 5:48:00 AM VNTR-based DNA Fingerprinting  Variable number of tandem repeats (VNTR) or minisatellites are located in noncoding regions of the genome  They are made up of DNA sequences between 15 and 100 bp long  Each unit is repeated several times  Repeats vary from person to person  VNTRs are useful in DNA profiling because there are as many as 30 different possible alleles at any VNTR in a population        If four different VNTR loci were examined. It is hybridized with a radioactive probe that recognizes DNA sequences within the VNTR region. thus enabling the generation of DNA profiles The majority of forensic DNA profiling is done using commercial kits that amplify regions of the DNA known as microsatellites or short tandem repeats (STRs)  STRs are similar to VNTRs.

or from male siblings Even two unrelated males may share the same Y profile. every 500 to 1000 nucleotides  Forensic SNP profiling involves only one nucleotide of a DNA molecule. STR profiling of the Y chromosome DNA is useful There are more than 200 STR loci on the Y chromosome. but less than 20 are used for forensic analysis PCR amplification uses specific primers that do not amplify DNA on the Y chromosome A major problem with Y chromosome profiling is that it cannot differentiate between DNA from fathers and sons. the probability that the two profiles are a random match is calculated      .    In cases where several men may be suspects.8)  SNPs occur randomly throughout the genome and on mtDNA. further investigation is done To determine the significance of any DNA profile match. the first step is to match the suspect's profile to those from an evidence sample or profiles already present in the DNA database If the profile does not match. if they share a distant male ancestor  The Y chromosome profiles are useful in genealogy studies and for missing persons Mitochondrial DNA Profiling:  Mitochondria contain one or more 16-kb circular DNA chromosomes  Mitochondria are passed to offspring via the human egg cell and therefore follow maternal inheritance Single-Nucleotide Polymorphism Profiling Single-nucleotide polymorphisms (SNPs) are single-nucleotide differences between two DNA molecules: base pair differences or small insertions or deletions (ST Figure 1. which makes SNP analysis suitable for analyzing DNA samples that are severely degraded Uniqueness of DNA Profiles  In a forensic investigation. the suspect is excluded If the profile does match.

law enforcement agencies in North America use a core set of 13 STR loci to generate DNA profiles The frequency of this profile would be 1 in 10 billion An exception to this uniqueness would be identical twins who share identical DNA and therefore identical profiles When DNA profiles come from two closely related people.      The profile probability or random match probability method gives a numerical probability that a person chosen at random from a population would share the same DNA profile as the evidence or suspect profile By increasing the number of loci analyzed in a DNA profile. CYP2E1.2) Cytochrome P450 family of proteins is particularly significant and is encoded by 57 different genes The products of the CYP2A6. about 2 million people in the United States have serious side-effects from pharmaceutical drugs. CYP2D6. CYP2B6. CYP2C9. and CYP3A4 genes are responsible for metabolizing most important pharmaceutical drugs. the profile probabilities must be adjusted Personalized Medicine & Pharmacogenomics: Pharmacogenomics is the study of how an individual’s entire genetic makeup determines the body’s response to drugs Optimizing Drug Therapies:  Pharmacogenomics increases the efficacy of drugs by matching drugs to subpopulations of patients who will benefit  Personalized pharmacogenomics is widely practiced in the diagnosis and treatment of cancers Reducing Adverse Drug Reactions:  Every year. . and approximately 100.000 people die  The costs associated with these adverse drug reactions (ADRs) are estimated to be $136 billion annually    Sequence variations in a large number of genes can affect drug responsiveness (ST Table 2. CYPC19. smaller probabilities of a random match are obtained Presently.

heart disease. other people have variants that cause drugs to be eliminated quickly.venter/#cnnSTCTex t o Know name of person and 3 sequenced genes for EXTRA CREDIT. deletions. there were genetic tests for approximately 2000 different diseases Diagnostic Tests: detect presence or absence of gene variants linked to suspected genetic disorder in symptomatic patient Predictive Tests: detect a gene mutation in patients with a family history of having a known disorder Carrier Tests: help identify patients carrying a mutation linked to a disorder that may be passed to offspring Prenatal Tests: detect potential genetic disease in a fetus Preimplantation Tests: performed early on embryos in order to select embryos that do not carry a suspected disease Genomic sequencing. and diabetes http://www. and duplications. and genome-wide association studies (GWAS) are beginning to reveal some of the DNA variants that may contribute to the risk of developing multifactorial diseases such as cancer. leading to reduced effectiveness  The FDA approved (2005) the use of a microarray gene test (AmpliChip®) that detects 29 genetic variants of CYP2D6 and CYP2C19 (ST Figure 2. Personalized Medicine & Disease Diagnosis        As of 2009.cnn. SNP identification.People with some gene variants metabolize and eliminate drugs slowly. which can lead to accumulations of the drug and overdose side-effects  In contrast. know disease he is at high risk for Epigenetics Introduction:  An epigenetic trait is a stable.4)  Detects mitotically and meiotically heritable phenotype that results from changes in gene expression without alterations in the DNA sequence   .

and tissue-specific patterns of gene expression The epigenome refers to the epigenetic state of a cell .  Epigenetics is the study of the ways in which these changes alter cell.

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GEN 3020: Ch. and analyze data related to Gene structure  Gene sequence and expression  Protein structure and function . 21 12/6/2013 5:48:00 AM Genome: complete set of DNA in a single cell of an organism Genomics: the study of genomes. share. allows the sequencing of entire genomes  Structural-focused on sequencing genomes  Clone-by-clone method and whole-genome shotgun method o Shotgun method involves shearing genes  Sanger method?  Hilo base gel? Bioinformatics: uses computer-based approaches to organize.

GenBank is one of the most important genomic databases  It is maintained by the National Center for Biotechnology Information (NCBI)  Each sequence deposited in GenBank receives an accession number Annotation: the process of identifying:  Genes  Their regulatory sequences  Their functions BLAST (Basic Local Alignment Search Tool):  a software application used to compare a segment of genomic DNA to sequence throughout the major databases to identify portions that align with or are the same as existing sequences Functional genomics:  The study of gene functions based on the resulting RNAs or possible proteins they encode as well as regulatory elements Human Genome project: project to learn major functions of the human genome  Less than 2% of genome codes for a protein  Many genes code for multiple protein through alternative splicing Functional categories have been assigned for human genes based on:  Function  Comparison to known genes and predicted protein sequences from other species  Predictions based on annotation and analysis of protein functional domains and motifs Areas of biological research having an ―omics‖ connection are continually developing  Proteomics  Metabolomics  Metagenomics (environmental)  Transcriptionomics  Nutrigenomics (new field) Comparative genomics:  compares the genomes of different organisms in order to answer questions about genetics and other aspects of biology .

Transcriptome analysis or global analysis of gene expression studies the expression of gene .

GEN 3020: Ch. 22 12/6/2013 5:48:00 AM .

the number of phenotypic classes in the F2 increases  2n + 1 (where n is the number of loci) Determining Gene Number for a Polygenic Characteristic:  #F2 that resemble each of the original homozygous parents  (1/4)^n Number of Categories (Phenotypes) Possible in the F2 Results of a Polygenic System:  2n+1 (where n is the number of loci) Additive effect of each allele:  (Maxp1-MinP2)/#allele (2 X gene#) Heritability Is Used to Estimate the Proportion of Variation in a Trait That Is Genetic: 2 types  Broad-sense heritability: H2= VG/VP  Narrow-sense heritability: h2=VA/ VP  Genetic variance = VG  Additive genetic variance = VA Phenotypic Variance (VP)  Environmental variance (VE)  Genetic-environmental interaction variance (VGE)       Obtained when the effect of a gene depends on the specific environment in which it is found.  As the number of loci affecting a character increases. Difference: is in the number of loci that determine the characteristic. 23 12/6/2013 5:48:00 AM Continuous (quantitative) characteristics:  Encoded by genes at many loci  Usually also affected by environment Polygeny: genes at many loci influence single characteristics Multiple-gene hypothesis for quantitative inheritance: each gene  Individually behaves in a Mendelin fashion  Contributes to the phenotype in a cumulative/quantitative way. VP = VG + VE + VGE VG = VA + VD + VI VP = VA + VD + VI + VE + VGE VD: dominance genetic variance VI: genic interaction variance (interaction between genes at different loci) .GEN 3020: Ch.

.  Analyzing parent–offspring regression.  Knowing the heritability of a trait has great practical importance because it allows statistical predictions regarding the phenotypes of offspring to be made on the basis of the parent’s phenotype.  Comparing individuals having different degrees of relatedness.Calculating Heritability:  Eliminating one of the variance components.