Theme: Fundamentals of human genetic

Plan of lecture:

• Introduction to Genetics and heredity• Gregor Mendel – a brief bio• Genetic terminology • Monohybrid crosses• Patterns of inheritance• Dihybrid crosses• Test cross• Gene interactions

Introduction to Genetics

• GENETICS – branch of biology that deals with heredity and variation of organisms

• Chromosomes carry the hereditary information (genes)

• Arrangement of nucleotides in DNA

• DNA RNA Proteins

Gregor Johann Mendel• Austrian Monk, born in what is now

Czech Republic in 1822• Son of peasant farmer, studied

Theology and was ordainedpriest Order St. Augustine.

• Went to the university of Vienna, where he studied botany and learned the Scientific Method

• Worked with pure lines of peas for eight years

• Prior to Mendel, heredity was regarded as a "blending" process and the offspring were essentially a "dilution"of the different parental characteristics.

•Mendel looked at seven traits or characteristics of pea plants

• In 1866 he published Experiments in Plant Hybridization, (Versuche über Pflanzen-Hybriden) in which he established his three Principles of Inheritance

• He tried to repeat his workin another plant, but didn’twork because the plantreproduced asexually! If…

• Work was largely ignored for34 years, until 1900, when 3 independent botanists rediscovered Mendel’s work.

• Mendel was the first biologist to use Mathematics – to explain his results quantitatively.

• Mendel predicted

The concept of genes

That genes occur in pairs

That one gene of each pair ispresent in the gametes

• Human genetics is the science that learns the peculiarities of the hereditary and variability in human organism

• Heredity – is the transmission of characteristics from parent to offspring through the gametes

Genetics terms you need to know:

• Inheritance – is the way of passing of hereditary information which depends on the forms of reproduction

During asexual reproduction the main traits are inherited through spores or vegetative cells, that's why the maternal and daughter cells are very similar.

During sexual reproduction the main traits are inherited through gametes.

Genetics terms you need to know:

Genetics terms you need to know:Gene – a unit of heredity; a section of DNA

sequence encoding a single proteinGenotype – is the genetic constitution of an

organism (a diploid set of genes)Genome – is a collection of genes of an

organism in sex cells (a haploid set of genes)

Alleles – two genes that occupy the same position on homologous chromosomes and that cover the same trait (like ‘flavors’ of a trait)

Locus – a fixed location on a strand of DNA where a gene or one of its alleles is located

Homozygous – having identical genes (one from each parent) for a particular characteristic.

Heterozygous – having two different genes for a particular characteristic.

Dominant – the allele of a gene that masks or suppresses the expression of an alternate allele; the trait appears in the heterozygous condition.

Recessive – an allele that is masked by a dominant allele; does not appear in the heterozygous condition, only in homozygous.

Genetics terms you need to know:

Dominant allele is symbolize with a capital letter

Recessive allele is symbolize with the corresponding small letter

If both alleles are recessive, the individual is homozygous recessive aa

An individual with two dominant alleles is homozygous dominant AA

An individual with Aa alleles is a heterozygote

• Genotype – describes the organism’s alleles (the genetic makeup of an organisms)

• Phenotype – the physical appearance

of an organism (Genotype + environment)

• Monohybrid cross: a genetic cross involving a single pair of genes (one trait); parents differ by a single trait

P = Parental generation

F1 = First filial generation; offspring from a genetic cross

F2 = Second filial generation of a genetic cross

Monohybrid cross• Parents differ by a single trait (stem size)

• Crossing two pea plants that differ in stem size, one tall one short

T = allele for tall

t = allele for dwarf

TT = homozygous tall plant

t t = homozygous dwarf plant

P ♀T T ♂t t

Monohybrid cross for stem length:

T T t t (tall) (dwarf)

P = parentalstrue breeding,homozygous plants:

F1 generation is heterozygous:

T t (all tall plants)

Punnett square• A useful tool to do genetic crosses• For a monohybrid cross, you need a square

divided by four….• Looks like

a windowpane…We use the Punnett squareto predict the genotypes and

phenotypes ofthe offspring.

Punnett square• "split" the letters of the genotype for each

parent & put them "outside" the p-square

• determine the possible genotypes of the offspring by filling in the p-square

• summarize results (genotypes & phenotypes of offspring)

T t T t

T t

T t

T T

t

t

Genotypes:100% T t

Phenotypes:100% Tall plants

T T t t

1. The law of monotony of the first filial generation

A - yellow seed; a - green seed

P: ♀ AA x ♂ aaG (Gametes): A aF1: Aa (yellow)

During crossing two homozygous which are differ from each other by one trait all progeny in the first filial generation is monogyny as well as phenotypic and genotypic

2. The law of segregation A cross between plants obtained from F1 plants.P: ♀ Aa x ♂ AaG: A, a A, a F2 : AA; Aa; Aa; aa

From a pair of contrasting characters (alleles) only one is present in a single gamete and in F2 these characters are segregated in the ratio of three to one (3:1) by phenotype and 1:2:1 by genotype.

When gametes are formed in heterozygous diploid individuals, the two alternative alleles segregate from one another.

• Getting all yellow seeds was an interesting result in itself

• Having viewed these results, Mendel then let the F1 generation, was 6022 yellow seeds and 2001 green seeds.

Two things stand out. • green seeds disappeared in F1, but come

back in F2.• green seeds came back in F2 as a specific

proportion of the seeds as a whole.

• Today, we know that inheritance occurs by way of gametes, and that it is due to meiosis that each gamete carries only one factor for each trait.

• Today, we know that the genes within the gametes are unaffected by the somatic cells.

• Mendel's law of segregation is in keeping with a particulate theory of inheritance because individual and separate factors are passed on from generation to generation.

• It is the reshuffling of these factors that explains how variations come about and why offspring differ from their parents.

Human case: CF• Mendel’s Principles of Heredity

apply universally to all organisms.

• Cystic Fibrosis: a lethal genetic disease affecting Caucasians.

• Caused by mutant recessive gene carried by 1 in 20 people of European descent

• CF disease affects transport in tissues – mucus is accumulated in lungs, causing infections.

Inheritance pattern of CF If two parents carry the recessive gene of

Cystic Fibrosis (c), that is, they are heterozygous (Cc), one in four of their children is expected to be homozygous for cf and have the disease:

CC Cc

Cc

cc

C c

C

c

CC = normalCc = carrier, no symptomscc = has cystic fibrosis

Dihybrid crosses• Matings that involve parents

that differ in two genes (two independent traits)

For example, flower color:

P = purple (dominant)

p = white (recessive)

and stem length:

T = tall t = short

Dihybrid cross: flower color and stem length

TT PP tt pp (tall, purple) (short, white)

Possible Gametes for parents

T P and t p

F1 Generation: All tall, purple flowers (Tt Pp)

TtPp TtPp

TtPp TtPp

tp tp

TP

TP

Dihybrid cross F2

If F1 generation is allowed to self pollinate, Mendel observed 4 phenotypes

Tt Pp Tt Pp (tall, purple) (tall, purple)

Possible gametes:TP Tp tP tp

Four phenotypes observedTall, purple (9); Tall, white (3); Short, purple (3); Short white (1)

TTPP TTPp TtPP TtPp

TTPp TTpp TtPp Ttpp

TtPP TtPp ttPP ttPp

TtPp Ttpp ttPp ttpp

TP Tp tP tp

TP

Tp

tP

tp

Genotype ratios (9): Four Phenotypes:1 TTPP2 TTPp2 TtPP4 TtPp1 TTpp2 Ttpp1 ttPP2 ttPp1 ttpp

Dihybrid cross: 9 genotypes

Tall, purple (9)

Tall, white (3)

Short, purple (3)

Short, white (1)

Principle of Independent Assortment

• Based on these results, Mendel postulated the 3. Principle of Independent Assortment:

“Members of one gene pair segregate independently from other gene pairs during gamete formation”

Genes get shuffled – these many combinations are one of the advantages of sexual reproduction

Relation of gene segregation to meiosis…

• There’s a correlation between the movement of chromosomes in meiosis and the segregation of alleles that occurs in meiosis

Beyond Mendelian Genetics: Incomplete Dominance

Mendel was lucky!Traits he chose in thepea plant showed up very clearly…One allele was dominant over another, so

phenotypes were easy to recognize.

But sometimes phenotypes are not very obvious…

Incomplete Dominance

Snapdragon flowers come in many colors.

If you cross a red snapdragon (RR) with a white snapdragon (rr)

You get PINK flowers (Rr)! R R

R r

r r

Genes show incomplete dominance when the heterozygous phenotype is intermediate.

Incomplete dominance

Incomplete Dominance

When F1 generation (all pink flowers) is self pollinated, the F2 generation is 1:2:1 red, pink, white

R R R r

R r

r r

R r

R

r

Codominance

• Both alleles are equally dominant

• Heterozygotes express both alleles = distinct expression of the gene products of both alleles can be detected

• MN blood group• F2 genotype and

phenotype ratios are 1:2:1

Genotype Phenotype

LMLM M

LMLN MN

LNLN N

Multiple Alleles• Genes can be characterized by more than 2

alleles • Multiple alleles (>2) can be studied only in

populations, because any individual carries only 2 alleles at a particular locus at one time

• ABO blood groups – Each individual is A, B, AB, or O phenotype – Phenotype controlled by isoagglutinogen

marker on RBC– IA and IB alleles are dominant to the IO allele – IA and IB alleles are codominant to each

other

PhenotypePossible

Genotype

Antigen on RBC surface

Antibody Made in Plasma

A IAIO, IAIA A Anti-B

B IBIO,IBIB B Anti-A

AB IAIB AB Neither

O IOIO O Both

Importance of A, B, O blood group antigens in medicine

Transfusion compatibility

Blood type: Donate to: AB AB A A or AB B B or AB O O, A, B, AB

•Disease resistance

Resistance to cholera and other types of infant diarrhea:

AB > A > B > O

•Possible resistance to other diseases: malaria, syphillis, cancer

Continuous variation

• Continuous variation (polimery). Different dominant non-allele's genes affect on one trait, making it more expressive.

• Traits determined by more than one gene are polygenic - meaning "many genes" - or quantitative traits.

Continuous variation

• Usually, several genes each contribute to the overall phenotype in equal, small degrees.

• The combined actions of many genes produce a continuum, or continuously varying expression, of the trait.

• Example: Skin color is familiar example of polygenic trait in humans.

Skin color is quantitative trait, that are controlled by two pairs of genes A1a1, A2a2.

Let’s sign skin color as • A1A1A2A2 – very dark• A1A1A2a2 or A1a1A2A2 — dark• A1a1A2a2 — medium brown • A1a1a2a2 or a1a1A2a2 — light• a1a1a2a2 — white (pale skin).

TASK

A woman with white skin married a medium-brown man. What is the skin

color possible for their children?

P: ♀a1a1a2a2 ♂ A1a1A2a2

G: a1a2 A1A2, A1a2, a1A2, a1a2

F1: A1a1A2a2; A1a1a2a2; a1a1A2a2; a1a1a2a2

Pleiotropy• Often an individual allele will have more than

one effect on the phenotype. • Such allele is said to be pleiotropic.• Pleiotropic relationships occur because in

examine the characteristics of organisms; we are studying the consequences of the action of products made by genes.

• Pleiotropy occurs in genetic diseases that affect a single protein found in different parts of the body. This is the case for Marfan syndrome.

Marfan syndrome• Autosomal dominant defect in

elastic connective tissue protein called fibrillian

• Fibrillian is abundant in the lens of the eye, in the aorta, and in the bones of the limbs, fingers, and ribs

• Marfan syndrome symptoms include lens dislocation, long limbs, spindly fingers, and a caved-in chest

“He who likes to eat fruit must climb the tree”

(English proverb)

Thank you for attention !