Theme: Organism’s level of organization of genetic information. Gene interactions Lecturer: ass....

Theme: Organism’s level of organization of genetic

information. Gene interactions

Lecturer: ass. prof. Tatyana Bihunyak

Questions:

• Introduction to Genetics and heredity• Gregor Mendel – a brief bio• Genetic terminology • Monohybrid and dihybrid crosses• Patterns of inheritance• 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

1. DNA2. Gen

4. Genotype

5. Person

3. Chromosome7. Population

6. Family (generation)

Cell

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

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

Genetics terms you need to know:

diploid set of genes haploid set of genes

1 2 3 4 5 6 7

XX

8

9 10 11 12 13 14 15

17 18 19 20 21 22

16

1 2 3 4 5 6 7

X

8

9 10 11 12 13 14 15

17 18 19 20 21 22

16

Genotype Genome

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

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

P: ♀ Cc x ♂ CcG: C, c C, c F2 : CC; Cc; Cc; cc

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

True or False? 1.____Homozygous has identical genes for a

particular characteristic

2. ____Heterozygous forms one type of gametes

3. ____ Recessive allele masks the expression of an alternate allele

4._____ Cystic Fibrosis is dominant trait

5. _____ Members of one gene pair segregate independently from other gene pairs during gamete formation

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

Examples of incomplete dominance •A child with wavy hair as a result of one parent's curly hair and the other's straight hair.•Tay-Sachs disease is an example of the result of incomplete dominance because the gene that makes the antibodies only creates half of the necessary antibodies which creates a vulnerability in the individual to get Tay-Sachs.•One parent has a large lip protrusion, the other parent has a small lip protrusion and the child has an average lip protrusion.•One parent has a high voice, the other parent has a low-pitched voice, so the child has a voice of medium pitch.•Sickle cell disease is the result of incomplete dominance as those who have the disease carry 50% normal and 50% abnomal hemoglobin.•If a red tulip and a white tulip are cross pollinated they result is a pink tulip.•A person with big hands and a person with small hands have offspring with hands of average size.

Sickle cell disease is the result of incomplete dominance as those who have the disease carry 50% normal and 50% abnormal hemoglobin.

P: ♀ HbAHbA x ♂ HbSHbSG: HbA HbSF1 : HbAHbS

Sickling Cells

Polymers of hemoglobindeform red blood cells

Normal

Sickle

Incomplete dominance

Incomplete Dominance

RR - Curly Hair, rr- Straight Hair, Rr- Wavy Hair (Curly + Straight = Wavy)

RR R r

R r

rr

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

Task 1. Mother has I (o) group of blood, father has IV (AB). Can children inherit group of blood of one of their parents?

Task 2.The boy has I (o) group of blood, his sister has III (B). Which are their parents’ groups of blood?

So, you must know ABO blood type for

• *determining of the blood group;• *blood transfusion; • *in paternity suits

Blood type tests can never prove that a certain person is the parent of a particular child; they can determine only whether he or she could be

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

Another sets of cell surface markers on human red cells are the RH blood group antigens, named for the rhesus monkey in which they first described. •This trait (antigen) is controlled by a single allele pair in 1 chromosome. •The rhesus-positive allele Rh is dominant over the rhesus-negative allele rh. •About 85 % of adult humans have the Rh cell surface marker on their red blood cells, and are called Rh-positive (RhRh, Rhrh). •Rh-negative persons lack this cell surface marker because they are homozygous recessive for the gene encoding it (rhrh).

Hemolytic disease of the newbornIf an Rh-negative person is exposed to Rh-positive blood, the Rh surface antigens of that blood are treated like foreign invaders by the Rh-negative person’s immune system, which proceeds to make antibodies directed against the Rh antigens. This most commonly happens when an Rh-negative woman may have children who are Rh positive if the father is Rh positive.

RhRh, Rhrh = rhesus-positiverhrh = rhesus-negative

P: ♀ rhrh x ♂ RhRhG: rh Rh F1 : Rh

Hemolytic disease of the newborn

In the first pregnancy, this factor causes no complication, but during birth, blood cells of the child enter the mother’s bloodstream, where they induce the production of “anti-Rh” antibodies. Then, in subsequent pregnancies, antibodies from the mother pass to the fetus and cause its red blood cells to clump, leading to condition called erythroblastosis fetalis.

Hemolytic disease of the newborn (erythroblastosis fetalis)

Hemolysis leads to elevated bilirubin levels. After delivery bilirubin is no longer cleared (via the placenta) from the neonate's blood and the symptoms of jaundice (yellowish skin and yellow discoloration of the whites of the eyes) increase within 24 hours after birth. Like any other severe neonatal jaundice, there is the possibility of acute or chronic kernicterus. Profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress. The prenatal manifestations are known as hydrops fetalis; in severe forms this can include petechiae and purpura. The infant may be stillborn or die shortly after birth.

Hemolytic disease of the newborn (erythroblastosis fetalis)

Treatment

After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion with a blood type compatible with both the infant and the mother, sodium bicarbonate for correction of acidosis and/or assisted ventilation.

Hemolytic disease of the newborn (erythroblastosis fetalis)

Treatment

Rhesus-negative mothers who have had a pregnancy who are pregnant with a rhesus-positive infant are offered Rh immune globulin (RhIG) at 28 weeks during pregnancy, at 34 weeks, and within 72 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG.

Superdominance

one dominant allele in heterozygous has more expressive manifestation than in homozygous state

• Example: Dominant gene B determines brachydactyly (short fingers). Homozygous dominant persons with genotype BB don’t survive; they die in the embryonic stage.

Person with genotype Person with genotype BbBb

Epistasis one gene masks the phenotypic effect

of another entirely different gene• A pair of genes at one locus may prevent the

expression of a pair of genes at another locus.• Such genes are called epistatic genes.

• Color of some fowls is result of interaction between two non-allelic genes: C—gene of colored fowls, c—gene of white fowls, I—gene, that masks the phenotypic effect of gene C (epistatic gene), i—gene, that does not masks the phenotypic effect of gene C. When the CcIi fowls are inbred, F2 includes white and colored fowls in the ratio of 13:3.

P: ♀ CCII (white) x ♂ ccii (white) G: CI ci F1 : CcIi (white)

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 (MS)• 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

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

True or False? 1.____ Incomplete dominance if heterozygous

phenotype intermediate between the two homozygous

2. ____A human with 0 blood has both A and B antigenes

3. ____ Skin color is example of polygenic trait in humans

4. _____IA and IB alleles are codominant to each other

5. _____A single pleiotropic gene can affect several traits

Thank you for attention !