Genetics-paulino

GENETICS Aliw P. Paulino,M.D. Assistant Professor Department of Anatomy UST Faculty of Medicine and Surgery

Definition • Study of how genes bring about characteristics or traits of an individual and how these characteristics are inherited • Genes are segments of DNA molecule that control discrete

History • ANCIENT GREEKS – recognized the passage of both desirable and undesirable traits from one generation to another. • 1700-18000 - numerous medical accounts of inherited disorders in families appear.

• 1814 – Joseph Adams published guidelines for genetic counseling based on the transmission of specific characteristics of families, effects of consanguinity and inbreeding.

• 1865 – GREGOR MENDEL publish the laws of inheritance.

• 1888 – WALDEYER coined the term cell-cell transmission of chromosomes. • 1900 – Correus, Tschermark and de Vries proposed that chromosomes were the carriers of genetic materials.

• 20th Century, Genetics has focused on : 1. the identification and visualization of human chromosomes . 2. the delineation of DNA as the functional component of the gene. 3. the unraveling of defects at the

Human Chromosome • Diploid – double set of chromosomes • 23 pairs of chromosomes – 22 pairs ( autosomes ) – 1 pair (sex chromosomes )

• Male : 46 , XY • Female : 46 , XX

Theories of Heredity • Blending theory of heredity – hereditary traits of the parents blend together to produce the characteristics observed in the offspring – dominant model ( 19th century )

• Particulate theory of heredity each trait from the parent will remain unchanged in the offspring.

Gregor Mendel • Austrian monk who lived in the middle of the 19th century • Through his experiments , he proposed the two fundamental laws that govern the heredity of many characters in organisms • Provided a strong foundation for the

Mendel’s Experiment • An organism has two genes ( alleles) for each trait • The two genes may have both the same allele (homozygous ) or of different allele (heterozygous) • A sperm or an egg carries only one allele for each inherited trait • If heterozygous , one is fully expressed (dominant allele ) the

Definition of Terms • Gene – unit that determines the heritable trait • Discrete portions of DNA molecules

• Allele – alternative forms of gene • Homozygous – the genes has the same allele • Heterozygous – • Genotype – the actual genetic make up of an organism • Phenotype – the observable

Genotype and Phenotype • Blood groups Type A - AO , AA Type B – BO , BB Type O – OO Type AB - AB

MENDELIAN LAW OF INHERITANCE 2. LAW OF SEGREGATION • each trait is controlled by two factors or genes (one inherited from each parent) • pairs of genes segregate (separate) during gamete formation • the fusion of gametes at fertilization pairs genes once again • members of a pair of genes (alleles) segregate and go to

Mendelian Law of Inheritance

1. Law of Independent Assortment • Different pairs of genes are distributed to the offsprings in a random manner and independent of each other

Patterns of Inheritance • AUTOSOMAL – dominant – recessive

• SEX LINKED – X- linked – Y - linked

Autosomal Dominant Trait AA • One parent affected • Male and females will be equally affected Aa Aa • Homozygotes married to normal individual will have all their children affected

aa

Aa

Aa

Autosomal Dominant Trait Aa • The affected individuals will have affected offsprings in every generation Aa aa • Heterozygotes married to normal individuals will have their offsprings a 50% chance of being

aa

Aa

aa

Dominant Traits • Widow’s peak • Finger hair • Freckles • Double jointed thumb • Free earlobes • Bent little fingers • Cleft chin • Tongue rolling

Autosomal dominant disorders • Neurofibromatosis ( chromosome 17 ) • Huntington’s disease (chromosome 4 ) • Thalassemia • Tuberous sclerosis • Retinoblastoma

Autosomal Recessive • Neither or both parent manifest the trait • Both sexes are equally affected • Affected individuals married to heterozygotes will have half of their offsprings affected ( dominant

Aa

aa

Aa Aa aa

aa

Autosomal Recessive • Affected individuals married to normal persons will have heterozygous but clinically normal offsprings

AA

aa

Aa Aa Aa Aa

Autosomal Recessive • If parents are both heterozygous, about ¼ of the sibs are affected • To manifest the trait , the gene should be homozygous

Aa

Aa

AA Aa Aa aa

Recessive traits • Straight hairline • No finger hair • No freckles • Attached earlobe

Recessive Disorders • Tay – Sachs disease • Cystic Fibrosis • Phenylketonuria

CONSANGUINOUS MARRIAGE - Individual more likely is heterozygous - Increase possibility of producing offspring with recessive trait.

• DEGREES OF RELATIONSHIP : * 1ST degree relatives - refer to parent, siblings * 2nd degree relatives - uncles, aunts, nephews, nieces. * 3rd degree relatives – 1st cousins

• Relationship of Common Parent, child, sib

Proportion Genes in 1/2

Grandparent, grandchild, uncle aunt, nephew, niece, half-sib

1/4

First cousin, great-grandparent, great-grandchild

1/5

Second cousin Third cousin

1/16 1/32

Sex Linked Inheritance 2. X- LINKED DOMINANT a. at least one parent is affected b. both males and females are affected c. affected female transmits the trait to half of her sons and half of her daughters d. affected male transmits it to

X – linked Traits • Red /green colorblindness

Hemophilia

Hemophilia

X- Linked Recessive • no male to male transmission • affected male transmit the gene to all their daughters who are heterozygote (carriers) • heterogygous females will have half of their sons affected and half of their daughters who are heterozygotes • homozygous females will have all sons affected and all daughters who are heterozygotes

Y linked ( Holandric ) • mutant gene is located in the Y chromosome • observed only in males Example : - HYPERTRICHOSIS PINNAE AURIS

Y Linked Disorders • Klinefelter’s syndrome – 47 XXY , 48 XXYY • 47XYY syndrome • Y chromosome infertility – azoospermia (AZF) factor gene deleted

Genetic Disorders • BRCA1 / 2 – breast cancer • APC gene – colorectal cancer • PTEN gene – prostate cancer

Pedigree Information

Thank You !!!