Genetics 2007
Genetics 2007
Genetics 2007
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
Charles
y
HISTORY OF GENETICS
Germplasm Theory
y y
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
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
HISTORY OF GENETICS
Thomas
y
HISTORY OF GENETICS
Oswald
y
James
Crick
y
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
APPLICATIONS OF GENETICS
Selective breeding
Legal Applications
Dispute in parentage y Identification of criminals
y
Genetic Counseling
y
Medicine
y
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
Eukaryotes
y
THE CELL
CHROMOSOME
CELL DIVISION
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
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
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
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
MEIOSIS II
Prophase II
y
Metaphase II
Spindle fibers formed y Chromosomes align
y
Anaphase II
y
Telophase II
Chromosomes uncoil y Nuclear membrane reappear
y
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
44 + XX
44 + XY
Genotype
y
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
cc
gamete
CC
cc
F1 gamete F2
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
zygote
DOMINANCE RELATIONSHIP
Incomplete
y
dominance
Overdominance
y
Codominance
y
MULTIPLE ALLELES
ABO blood groups Type A
y
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
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
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 EFFECTS
External
y
factors
Internal factors
Age y Sex
y
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
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
Sex
y
Heterogametic species has lower crossover frequency Inversely proportional to crossover Directly proportional
Nutrition
y
Maternal age
y
Chemical effects
y
Temperature
y
Cytoplasmic effect
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
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
CONCEPT OF A GENE
Chromosome
y
Components
y
DNA RNA
Proteins
Basic proteins: histones or protamine Non-histone chromosomal proteins (acid proteins) Lipids
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
Beads on
Histones
Metaphase chromosome
But
How?
DNA REPLICATION
Two strands of DNA serves as template or pattern to which complimentary strand is synthesized Accuracy of replication
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
INITIATION OF REPLICATION
4. Initiation of DNA synthesis
RNA primase y RNA primer (3 OH end)
y
INITIATION OF REPLICATION
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
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
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
tRNA y rRNA
y
RNA TRANSLATION
Activation of amino acid Amino acid + tRNA ATP and amino acyl synthetase enzymes
INITIATION OF TRANSLATION
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
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
TERMINATION OF TRANSLATION
Release factors UAA, UAG, UGA
Inborn errors of Metabolism Gene controls/influence the phenotype Impaired function of the enzyme that is usually active at a particular metabolic step
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
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
How one cellular genotype gives rise to many different cellular phenotypes?
Determination
y
A cell makes an irreversible commitment to follow a specific developmental path The expression of cells specialized role
Differentiation
y
PRE-TRANSCRIPTIONAL CONTROL
Euchromatin
Active chromatin y Condensed
y
Heterochromatin
Inactive chromatin y Decondensed
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
SD Allele on kidney development Pituitary dwarfism Melanophores from embryonic nerve cord to developing skin
MUTATIONS
MUTATION
Euploidy
y
Aneuploidy
y
One or more chromosomes of a normal set (genome) are lacking or are present in excess
TYPES OF ANEUPLOIDS
Type Formula Chromosome Number : Complement Configuration at Diakenesis
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
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
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:
C. GENE MUTATIONS
Types:
y
Base pair
Transition Transversion
Transition
y
Transversion
y
A by G
y
A by T T by A
T by C
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
D. REVERSE MUTATION
MUTAGENIC AGENTS
Ionizing radiation Chemical Mutagens Exposure to extreme conditions Cell regeneration Hybridization
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
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
AUTOSOMAL ANEUPLOID
Male
Deletion Examples
y
Translocation Example
y
Cri-du-chat Syndrome
Down Syndrome
5 p (short arm of 5)
y
Muscular Dystrophy
Patau Syndrome
Alagille Syndrome
Philadelphia (T(22q;9q))
Galactosemia
Homozygous recessive (gg) y Deficient in Gal-1-P uridyl transferase
y
Phenylketonuria
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
Bipolar Disorder
Chromosomes 4, 10, 18 and 22 y Maternal inheritance
y
THANK YOU