GENETICS: THE SCIENCE OF HEREDITY AND VARIATION

Jay Anthony O. Caete, PTRP, MSc RTR Medical Foundation Tacloban City

DEFINITION
1906,

William Bateson Greek word gen meaning to become or to grow into something Genetics Science of Heredity and Variation
Heredity transmission of traits from generation to generation y Variation genetic differences between organisms
y

HISTORY OF GENETICS
Theory of Pangenesis y 19th century y Aristotle (384 322 BC) y Semen was formed everywhere in mans body and such semen reflected the characteristics of the body part from where it was formed y Semen traveled through the blood vessels into male reproductive organs

HISTORY OF GENETICS
Theory
y

of Inheritance of Acquired Characteristics

Jean Baptiste de Lamarck (1744 1829) y Use and Disuse of Characteristics

Charles
y

Darwin (1809 1882)

Follows the Theory of Pangenesis

HISTORY OF GENETICS

Germplasm Theory
y y

August Weisman (1834 1914) Experiment:

Cut the tail of mice from generation to generation but produces an offspring with normal tail Inheritance of tail length did not depend on the particles produced on the tail of parent mice; but rather on the germplasm

Conclusion:

Germplasm or sex cells perpetuated themselves in reproduction generation after generation Somatoplasm or cells of all other body parts were produced be the germplasm only as a means to protect and reproduce itself

HISTORY OF GENETICS

Kolreuter
y

Hybrids between species might have shown uniform appearance but their fertile offsprings would usually produce considerable diversity Same experiment but on plants

Gartner, Naudin, Darwin

y

Gregor Mendel
Father of Genetics y Appearance of different characters in heredity followed specific laws that could be determined by counting the diverse kinds of offsprings produced by particular set of crosses
y

HISTORY OF GENETICS

Carl Correns (Germany), Erick Von Tschermak (Austria), and Hugo de Vries (Netherlands)
y

Duplicated Mendels work (plants) Duplicated in animals

Bateson, Saunders and Cuenot

y

Walter S. Sutton (USA) and Theodor Boveri (Germany)

1903 y Association of Mendelian factors with the Chromosomes
y

HISTORY OF GENETICS
Thomas
y

Hunt Morgan (1910) and Calvin Morgan (1916)

Chromosome Theory of Inheritance y Discovery of the sex chromosomes and specific chromosomes y Each chromosome contains not one but many genes

HISTORY OF GENETICS
Oswald
y

T. Avery, Collin M. McLeod, and Maclyn McCarty

Identified DNA as hereditary material

James

D. Watson and Francis H. C.

Crick
y

Discovers molecular structure and chemical properties of DNA

DNA foundation for the principles of heredity

SCOPE OF GENETICS

Individuals
y

Development of and maintenance of its own unique, inherent pattern Ability to transfer these systems to other generations for continued existence Variety of patterns and changes over geological time

For the species

y

For all living forms

y

APPLICATIONS OF GENETICS

Plant, Animal and Microbial Improvement

y

Selective breeding

Legal Applications
Dispute in parentage y Identification of criminals
y

Genetic Counseling
y

Inheritance of desirable or undesirable characteristics Identification of diseases and preventive measures

Medicine
y

THE PHYSICAL BASIS OF HEREDITY

The Chromosome

THE CELL

Two parts
y

Cytoplasm

Major portion of the protoplasmic substance contained in the cell membrane Dark staining body within the cytoplasm

Nucleus

Prokaryotes
y

Nuclear membrane is absent Presence of nuclear membrane

Eukaryotes
y

THE CELL

CHROMOSOME

CELL DIVISION

Gives rise to a new cell Mechanism for genetic transmission Types:

y

Mitosis

Genetic and chromosome composition of a cell is faithfully reproduced in each of the daughter cells Multicellular organism, repair Unicellular organism, reproduction Chromosome number of the cells is reduced into half of its usual number Multicellular organism, reproduction

Meiosis

CELL CYCLE

Interphase
G1 period of growth before DNA is replicated y S DNA replication y G2 cell prepares for cell division
y

M phase
Meiosis y Mitosis
y

INTERPHASE

G1 phase
Longest phase of the cell cycle y Cell increases its volume
y

S phase
y

DNA replication or synthesis RNA and protein synthesis necessary for chromosome synthesis

G2 phase
y

MITOSIS

Prophase
Chromosomes shorten, thicken and become visible as thick rods y Chromatid formation
y

Metaphase
y

Chromosomes align at the equatorial plane through the centromere Chromosomes move toward opposite poles Chromosomes regroup

Anaphase
y

Telophase
y

Cytokinesis (cell plate formation or cleavage formation

MEIOSIS

Meiosis I (reductional)
y

Meiosis II (equational)
Prophase II y Metaphase II y Anaphase II y Telophase II
y

Prophase I
Leptonema Zygonema Pachynema Diplonema Diakinesis

Metaphase I y Anaphase I y Telophase I

y

PROPHASE I

Leptonema
y

Pachynema
y y

Chromosomes appear long thin threads Pairing of homologous chromosome Essential for crossing over

Zygonema
y y

Further coiling Crossing over between sister and non-sister chromatids Separation of homologues starting at centromere Bivalents are maximally condense Nuclear membrane disappear

Diplonema
y

Diakinesis
y y

Metaphase I
y

Bivalents align at the equatorial plane

Anaphase I
Univalents in each bivalent separate from each other y Accounts for reductional phase of meiosis I
y

Telophase I
Chromosomes regroup y Nuclear membrane reappear
y

Interkinesis transitional stage

MEIOSIS II

Prophase II
y

Chromosomes begin to condense

Metaphase II
Spindle fibers formed y Chromosomes align
y

Anaphase II
y

Sister chromatids of a univalent separate toward the pole

Telophase II
Chromosomes uncoil y Nuclear membrane reappear
y

Cytokinesis forming four cells with haploid chromosome number

CONSEQUENCES OF MITOSIS VS. MEIOSIS

Mitosis
y

Meiosis I
y

Chromosomes are reproduced and transmitted equally to the daughter cells The gene retains its individuality

Each daughter nucleus contains half the chromosome number of the parental cell Each may have different genetic composition Two daughter nuclei of meiosis I undergo mitosis, producing four haploid nuclei

Meiosis II
y

EUKARYOTIC LIFE CYCLE

44 + XX

44 + XY

GENE SEGREGATION AND

INTERACTION

Genotype
y

Genetic constitution of an individual

Phenotype
Appearance of an individual y Morphology, physiology and behavior
y

LAW OF SEGREGATION
The unit of hereditary characteristics occur in pairs In formation of gametes, these segregates so that only one member goes into particular gamete Dominant VS. Recessive Example

CC curly hair y cc straight hair

y

CURLY VS. STRAIGHT HAIR

parent

CC

cc

gamete

CC

cc

F1 gamete F2

Cc C C C c CC (curly) Cc (curly) c c Cc (curly) cc (straight)

LAW OF INDEPENDENT ASSORTMENT

Genes for different characters are inherited independently of one another or that the members of one pair of alleles segregate independently of the other pair Example

CCRR curly rough hair y ccrr straight smooth hair

y

EXAMPLE
parent

CCRR

ccrr

gamete

CR

cr

F1 gamete F2

CcRr CR CR CR Cr cR cr CCRR CCRr CcRR CcRr Cr Cr CCRr CCrr CcRr Ccrr cR cR CcRR CcRr ccRR ccRr cr CcRr Ccrr ccRr ccrr cr

SEGREGATION AND ASSORTMENT OF HAPLOID

ORGANISM
gametes
Y+ Y+ Y Y

zygote

DOMINANCE RELATIONSHIP
Incomplete
y

dominance

Red + White = Pink

Overdominance
y

Heterozygotes contains more than homozygotes

Codominance
y

M-N blood types M MM M Anti-N N NN N Anti-M MN MN M;N none

MULTIPLE ALLELES
ABO blood groups Type A
y

Genotype AA, AO Genotype BB, BO Genotype AB Genotype OO

Type B
y

Type AB
y

Type O
y

LETHAL GENES

Recessive lethal
Lethal when in homozygous recessive y Xeroderma pigmentosum y Infantile amaurotic idiocy
y

Dominant lethal
Lethal when in homozygous and heterozygous y Epiloia y Huntingtons disease
y

Penetrance of lethal genes Environmental influence on lethal genes

MODIFIER GENES
Changes the phenotypic effects of other genes in quantitative fashion Dilution or enhancement Suppressors Dominant or recessive

GENE INTERACTIONS

Novel phenotypes
y

New phenotypes result from interaction between dominants, and also from interaction between both recessives Complete dominance in both gene pairs, but one gene, when homozygous recessive, hides or masks the effects of the other Complete dominance in both gene pairs, but one gene, when dominant, masks the effect of the other

Recessive Epistasis
y

Dominant epistasis
y

GENE INTERACTIONS

Complementary genes
y

Complete dominance in both gene pairs, but either recessive homozygote is epistatic to the effects of the other gene Complete dominance in both gene pairs , but either gene, when dominant is epistatic to the other

Duplicate gene
y

ENVIRONMENTAL INFLUENCE ON GENE

EXPRESSION

Penetrance
y

Proportion of genotypes that show an expected phenotype Degree to which a particular phenotypic effect is expressed by the individual

Expressivity
y

Pleiotropy
One gene has multiple phenotypic effect y PKU phenylalanine (blood, head size, hair color)
y

Phenocopy
y

Environmental mimic of gene action

ENVIRONMENTAL EFFECTS
External
y

factors

Internal factors
Age y Sex
y

Temperature y Light y Nutrition y Maternal relations Blood incompatibility

Sex linked traits Diabetes mellitus

Substrates

AGE
Genetic trait Alcaptonuria Infantile amaurotic idiocy Vitamin D resistant rickets Muscular dystrophy Juvenile amaurotic idiocy Periodic paralysis Pattern baldness Diabetes mellitus Usual age of onset Birth 4-6 months 1 year 2-5 years 5-10 years 10 years 20-30 years 40-60 years

LINKAGE AND RECOMBINATION

LINKAGE
The physical association of genes in the same chromosome Tendency to be inherited together Crossing over Types:
y

Complete linkage

When two genes are closely located in linear order on the same chromosome When the genes are far apart from each other

Incomplete linkage

FACTORS AFFECTING RECOMBINATION

Sex
y

Heterogametic species has lower crossover frequency Inversely proportional to crossover Directly proportional

Nutrition
y

Maternal age
y

High calcium decreases crossingover Antibiotics increases crossing-over

Chemical effects
y

Temperature
y

Cytoplasmic effect

Radiation Chromosome structure Centromere

SEX DETERMINATION
Sexuality theory Hartman (1931) Every cell of sexual reproducing organism was bisexual It has a potential for the male and female sex, becoming male or female by the development of one or the other potential Bisexual, hermaphrodite, sex reversal, and intersex

SEX DETERMINATION Genetic sex determination Environmental sex determination Chromosomal sex determination

XX XY system y Single active X chromosome y Presence of Barr body during interphase y Lyonization
y

SEX LINKAGE
X linked inheritance Hemophilia Recessive

Y linked inheritance Porcupine man

SOME X-LINKED CHARACTERISTICS

Color blindness Muscular dystrophy G6PD Hypochromic anemia Absence of central incisor Congenital deafness Mental deficiency Spinal ataxia Parkinsonism

Ocular albinism Myopia Congenital cataract Retinitis pigmentosa Congenital aldrenal hypoplasia Diabetes insipidus Albinism deafness syndrome

SOME Y-LINKED CHARACTERISTICS

Webbed toes Hypertrichosis

CHEMICAL BASIS OF HEREDITY

CONCEPT OF A GENE

CHEMICAL COMPOSITION OF CHROMOSOME

Chromosome
y

Carriers of the genetic material Nucleic acid

Components
y

DNA RNA

Proteins

Basic proteins: histones or protamine Non-histone chromosomal proteins (acid proteins) Lipids

DNA AS GENETIC MATERIAL

H.J. Muller (1922) Characteristics
y y y y y y

Duplicates itself with extraordinary fidelity Structure must be very stable Error or mutation is duplicated faithfully as the original Capacity to carry necessary biological information Ability to transmit information from gen to gen Information stored and carried must be decoded and translated into action

CHEMICAL COMPOSITION OF DNA

James D. Watson and Francis H.C. Crick (1953)

MOLECULAR STRUCTURE OF DNA

ORGANIZATION OF DNA IN CHROMOSOMES

ORGANIZATION OF DNA IN CHROMOSOMES

DNA double helix (2-nm diameter)

Beads on

Histones

a string Nucleosome (10-nm diameter)

Tight helical fiber Supercoil (30-nm diameter) (200-nm diameter)

Metaphase chromosome

MODE OF DNA REPLICATION

But

How?

CENTRAL DOGMA OF GENETICS

DNA REPLICATION
Two strands of DNA serves as template or pattern to which complimentary strand is synthesized Accuracy of replication

Specific base pairing y Exonuclease activity

y

Steps
Initiation y Elongation y Termination
y

INITIATION OF REPLICATION
1. Identification of the origin of replication
y y

ORE- origin of replication element (A-T rich region of DNA) DUE- DNA unwinding element

INITIATION OF REPLICATION
2. Unwinding of the double-stranded DNA to provide a single-stranded DNA template
y

helicases Helicase, primase, DNA polymerase , SSB protein

3. Formation of the Replication Fork

y

INITIATION OF REPLICATION
4. Initiation of DNA synthesis
RNA primase y RNA primer (3 OH end)
y

INITIATION OF REPLICATION

DNA Polymerase III

y

Catalyze the phosphodiester bond where nucleotides are added

Leading strand Lagging strand

ELONGATION OF THE COMPLEMENTARY STRAND

Elongates from 5 to 3 DNA polymerase III
y

Nucleotide triphosphates(dATP, dGTP, dTTP, dCTP)

Okazaki fragments DNA pol I

y

Proofreading Seals the gap

DNA ligase
y

TERMINATION OF REPLICATION
DNA replicated faithfully Two daughter DNA molecules that are exact copies of the parent DNA

RNA TRANSCRIPTION

Eukaryotes
y

Occurs in nucleus Occurs in cytoplasm

Prokaryotes
y

INITIATION OF TRANSCRIPTION

Sigma factor ( )
y

Recognizes the promoter sequence Attaches to promoter sequence or initiation point of the daughter DNA

RNA pol
y

ELONGATION OF THE TRANSCRIPT

RNA pol
Moves along the anticoding strand of the DNA y Brings an RNA nucleotides
y

A T (U) TA G C CG

TERMINATION OF TRANSCRIPTION

Rho factor ( )
Binds to RNA pol y RNA complementary strand is formed
y

Types of RNA
y

mRNA

Provides the RNA template (codon)

tRNA y rRNA
y

RNA TRANSLATION
Activation of amino acid Amino acid + tRNA ATP and amino acyl synthetase enzymes

INITIATION OF TRANSLATION

Initiation codon AUG Oriented at 5 end of the mRNA IF1

y

Attach the aa-tRNA complex with fmet to 30s subunit Binds mRNA to 30s subunit ad orients the fmet to AUG codon Binds 30s to 50 s sunit

IF3
y

IF2
y

GTP Peptidyl binding site (P-site) Amino acyl site (A site)

ELONGATION OF THE PEPTIDE CHAIN

Once fmet is set at the P site, EFTu + GTP, brings a new aa-tRNA complex to A site Peptidyl transferase

Present in 50s subunit y Catalyzes a peptide bond between fmet and subsequent amino acid y Releases the tRNA at P site to cytoplasm for reactivation
y

EF-G +GTP
y

Displaces aa-tRNA from A site to P site

TERMINATION OF TRANSLATION
Release factors UAA, UAG, UGA

GENE FUNCTION: PROTEINS AND ENZYMES

GENE ENZYME RELATIONSHIP

Inborn errors of Metabolism Gene controls/influence the phenotype Impaired function of the enzyme that is usually active at a particular metabolic step

ONE GENE ONE ENZYME HYPOTHESIS

Every gene controls a particular enzyme and that the ultimate product of a metabolic process was affected by a stepwise succession of enzymes, each produced by a particular gene

SOME INBORN ERRORS IN METABOLISM

SOME INBORN ERRORS IN METABOLISM

CONTROL OF SPECIFIC GENE EXPRESSION BY HORMONES

Each hormone affects only the target tissues

DEVELOPMENTAL GENETICS

DEFINED Studies the relationships between gene regulation and cell differentiation during development Development requires gene actions, considering that phenotypic trait is an expression of a genotype It involves irreversible programmed phenotypic events

DIFFERENTIAL GENE ACTION

How one cellular genotype gives rise to many different cellular phenotypes?

A. DIFFERENTIAL GENE ACTION

Determination
y

A cell makes an irreversible commitment to follow a specific developmental path The expression of cells specialized role

Differentiation
y

DIFFERENTIAL GENE ACTION

DIFFERENTIAL GENE ACTION

Pre transcriptional Control Transcriptional Control Translational Control Post Translational Control

PRE-TRANSCRIPTIONAL CONTROL

Euchromatin
Active chromatin y Condensed
y

Heterochromatin
Inactive chromatin y Decondensed
y

DNA methylation (inactive) Selective DNA replication

y

Gene amplification

TRANSCRIPTIONAL CONTROL

Differential initiation
y

TATA box

TRANSLATIONAL CONTROL

Polyadenylation
Poly A tail y Longer mRNA half-life
y

POST-TRANSLATIONAL CONTROL

Epigenetic modification
Deletion of a part of peptide chain y Changes in redox state affecting enzyme structure y Attachment of small molecular moiety of enzyne y Polymerization and combination of phosphate group
y

B. NUCLEOPLASMIC INTERACTIONS
Cell differentiation is based upon the differential activation of genes. Cytoplasm is composed of heterogenous substances. Differential activation.

Molecular exchanges between nucleus and cytoplasm. y Control of macromoecular synthesis in the nucleus by cytoplasm
y

C. GENES AND MORPHOGENESIS

Gene effects on systems of embryonic induction

y

SD Allele on kidney development Pituitary dwarfism Melanophores from embryonic nerve cord to developing skin

Gene effects on endocrine systems

y

Gene effects on migrating cells

y

Gene effects on the regulation of growth and metabolism

MUTATIONS

MUTATION

Changes in the organism that are heritable and essentially permanent

A. Variation in Genome Structure or Numerical Changes of the Chromosomes y B. Changes in Chromosome Structure or Chromosomal Aberrations y C. Gene Mutations y D. Reverse Mutations
y

Mutagenic Agents Evolutionary Significance of Mutations

A. Variation in Genome Structure or Numerical Changes of the Chromosomes

Euploidy
y

Changes involving the whole genome or the entire set of chromosomes

Aneuploidy
y

One or more chromosomes of a normal set (genome) are lacking or are present in excess

VARIATIONS IN CHROMOSOME NUMBER

Type Monoploid Diploid Autotriploid Autotetraploid Allotetraploid Formula n 2n 3n 4n 4n Chromosome Complement (1234) (1234) (1234) (1234) (1234) (5678) (1234) (1234) (1234) (1234) (1234) (1234) (5678)

TYPES OF ANEUPLOIDS
Type Formula Chromosome Number : Complement Configuration at Diakenesis

Monosomic Nullisomic Double Monosomic Trisomic Tetrasomic Double Trisomic

2n 1 2n 2 2n 1 1 2n + 1 2n + 2 2n + 1 + 1

7 : (ABCD) (ABC) 6 : (ABC) (ABC) 6 : (ABCD) (AB) 9 : (ABCD) (ABCD) (A) 10 : (ABCD) (ABCD) (A) (A) 10 : (ABCD) (ABCD) (AB)

3III, 1I 3II 2II, 2I 3II, 1III OR 4II,1I 3II, 1IV OR 5II 2II, 2III OR 4II, 2I

B. Changes in Chromosome Structure or Chromosomal Aberrations Chromosome number remains the same but its genetic material becomes altered Break in the chromosome

Ununited y Reunited y Exchange with other ends

y

Types:
Deletion y Duplication y Inversion y Reciprocal Translocation
y

DELETION

Types
y

Interstitial

Example: Philadelphia 22
y y

Centromeric Non-centromeric

y y y y y

Terminal

Long arm of chromosome 22 Myeloid leukemia Short arm of chromosome 5 Cat-like cry, mental retardation, physical defects

Effects
Lethality Pseudo-dominance No crossing over Unique phenotype

Cri-du-chat syndrome
y y

DUPLICATIONS

Types
Tandem y Reverse tandem y Displaced
y

Homobrachial Heterobrachial

Transposition to nonhomologue y Extra chromosome

y

INVERSION

Types
Paracentric y Pericentric
y

Consequences
Normal y Sterile
y

RECIPROCAL TRANSLOCATION
Single breaks in two nonhomologous chromosomes produce an exchange of chromosome sections between them Types:

Homozygous translocation y Heterozygous translocation

y

C. GENE MUTATIONS

Types:
y

Base pair

Transition Transversion

Frameshift mutation y Mutator genes y Transposons or Jumping Genes

y

BASE PAIR SUBSTITUTION

Transition
y

Transversion
y

Purine with another purine

Purine with pyrimidine

A by G
y

Pyrimidine with another pyrimidine

A by T T by A

T by C

Pyrimidine with purine

G by C C by G

FRAMESHIFT MUTATION
Addition or deletion of a single nucleotide or a few nucleotides Shift in reading frame Usually in regions where there is monotonous DNA sequence

AAAAAAA y TTTTTTT
y

MUTATOR GENES

Associated with DNA polymerase or similar enzymes involved in DNA replication and repair
Treffers mutator gene y Changes A T pair to C G during replication
y

TRANSPOSONS OR JUMPING GENES

Genes that are capable of moving around the DNA Able to control the DNA where it attaches

D. REVERSE MUTATION

Mutant genotype is changed into wild type genotype

MUTAGENIC AGENTS
Ionizing radiation Chemical Mutagens Exposure to extreme conditions Cell regeneration Hybridization

EVOLUTIONARY SIGNIFICANCE OF MUTATION

Genetic variability Coping with the environmental change

DELAYED CHROMOSOMAL AND EXTRACHROMOSOMAL INHERITANCE

DELAYED CHROMOSOMAL AND EXTRACHROMOSOMAL INHERITANCE

Patterns entirely different from segregation ratio Maternal transmission pattern Different hereditary process:

A. Delayed chromosomal inheritance y B. Extrachromosomal inheritance

y

A. DELAYED CHROMOSOMAL INHERITANCE

Dawdling effect due to the presence of maternal DNA

B. EXTRACHROMOSOMAL INHERITANCE
Plasmagenes, plasmons, cytogenes or plasmids Unlike, delayed chromosomal inheritance: they are capable of self-perpetuation, independent transmission do not disappear in subsequent generation Example:
y

Progressive external ophthalmoplegia

INTELLIGENCE?????

HUMAN GENETICS

CYTOGENETICS
Somatic cells = 46 chromosomes (2n = 46) 22 pairs autosomes + XX (female) 22 pairs autosomes + XY (male)

Group A B C D E F G Chromosome 1,2 and 3 4 and 5 6-12 and X 13, 14 and 15 16, 17 and 18 19 and 20 21, 22 and Y Size Large Large Medium Medium Short medium Short Very short Centromere Location Approx. median Submedian Submedian Acrocentric Median or submedian Approx. submedian acrocentric

ABNORMAL CHROMOSOME NUMBER

Polyploidy (triploidy) 17% of spontaneous abortion 3 % of stillbirths and newborn deaths Aneuploidy

Autosomal aneuploid y Sex chromosome aneuploid

y

AUTOSOMAL ANEUPLOID

Downs Syndrome (22II + XX/XY + I21)

Translocation of D or E group y Trisomic to 21
y

E Trisomy syndrome (22II + XX/XY + I16 or 17 or 18)

y

Edward syndrome (trisomic to 18) Patau syndrome (trisomic to 13)

D Trisomy Syndrome (22II + XX/XY + I13 or 14 or 15)

y

SEX CHROMOSOME ANEUPLOID

Turners Syndrome (22II + XO)

y

Female Male Female

Klinefelters Syndrome (22II + XXY)

y

Triplo X Syndrome (22II + XXX)

y

Jacob Syndrome or Double Y Syndrome (22II + XYY)

y

Male

Hermaphroditisim (46, XY)

ABNORMAL CHROMOSOME STRUCTURE

Deletion Examples
y

Translocation Example
y

Cri-du-chat Syndrome

Down Syndrome

5 p (short arm of 5)
y

Long arm 21 and 14 Duplication of 13 and 14 2 and 20

Muscular Dystrophy

Patau Syndrome

Deletion of dystrophin in chromosome X, leading to frameshift mutation

Alagille Syndrome

Philadelphia (T(22q;9q))

INBORN ERRORS OF METABOLISM

Galactosemia
Homozygous recessive (gg) y Deficient in Gal-1-P uridyl transferase
y

Phenylketonuria
y

Absent phenylalanine hydroxylase

Primaquine Sensitivity and Favism

X linked y Primaquine drug for malaria y Fava beans (hemolytic anemia)
y

PROTEIN ALTERATIONS DUE TO MUTATIONS

Sickle Cell Anemia

Hemoglobin A replaced by Hemoglobin S y Glutamic acid is replaced by valine in the sixth amino acid of the beta globin peptide chain
y

Thalassemia
Persistence of fetal hemoglobin y Few beta globin chain which are needed for hemoglobin synthesis
y

Cystic Fibrosis
y

Deletion of a single amino acid of the cystic fibrosis transmembrane regulator altering the chloride channels in epithelial cell membrane

PREDISPOSITION TO ALLERGY
Allergy gene in Chromosome 11 Gene for cell surface markers Essential for communication between different immune cells

BEHAVIORAL GENETICS

Schizophrenia
y

Chromosomes 1, 4, 6, 9 and 11 Dopamine and serotonin Dopamine D2 receptor Serotonin and/or norepinephrine

Eating Disorder
y

Drug Addiction
y

Major Depressive Disorder

y

Bipolar Disorder
Chromosomes 4, 10, 18 and 22 y Maternal inheritance
y

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