Mendelian & Non-Mendelian Genetics

Mendelian & non-Mendelian

GeneticsA class lecture for undergraduate

student

By:Purnomo SoeharsoDepartment of Medical Biology

Faculty of Medicine UI

Genetics : Knowledge/science about heredity.

Deal with:- How biological information (genes) and/or traits are transferred (transmitted) from one generation to the next. - How the information is expressed by the organism carrying the related (relevance) gene .

Benefit : - ilucidate pattern of inheritance. - allow genetic manipulation (selective mating or direct alteration of genetic substance) create new organism / species.

According to Denver and Patau classification, human chromosomes are classified into 7 groups based on their shape and morphology.

Banding Technique:

G banding

T banding

R banding

Chromosome Structure

Chromosome morphology:

1. Metacentric

2. Sub metacentric

3. Acrocentric

4. Telocentric

Mendel’s experiment :

Worked on pea plants (Pisum sativum) crosses, in consideration that :- their characters were readily observable and can be differentiated easily : red X white flowers tall X short trees smooth X wrinkled seeds- consist of complete flowers – contain either ♂ or ♀ sex cells /structures in 1 flower enable to conduct self fertilization as well as cross fertilization.- exist in a short life cycle generation shift runs quickly & detectable easily.- the plants are diploid segregate in simple manner

A cross of a highly inbred strain of peas produce progeny of 100% identical to the parents

Mating of inbred animals/plants in several generations inbreeding animals/plants of pure line carry similar heredity factor (genotype) and express the same characteristics in all generations. AA X AA aa X aa AA AA AA aa aa aa

A cross between two highly inbred strains of peas

P : tall tree (♂) X short tree (♀) DD dd

F1 : Dd (tall tree)

F2 : self fertilization Dd X Dd

♀ ♂

D d

D DD Dd

d Dd dd

F2 genotypes DD : Dd : dd = 1 : 2 : 1 F2 phenotype tall (D-) : short(dd) = 3 : 1

F1 are produced by P (♂ & ♀) segregation in the production ofD & d gametes the combination of the two gametes createplant with Dd genotype.

F2 are produced by F1 (♂) segregation in the production of D & d gametes, the same way for (♀) segregation in the production of D & d gametes the combination of these gametes is creating DD: Dd: dd = 1 : 2 : 1DD & Dd express the same phenotype the proportion of phenotype (D-) : dd = 3 : 1

The inheritance of a character (phenotype) is determined by parental genotypes, each of which inherit heriditary factors (genes).

Terminology

- the alternative form of gene D is its allele d

- D allele is dominant, while d allele is recessive the expression of D mask the expression of d provided both of them present in one individual.

- Individual with identical allelic pair (DD or dd) is having homozygote genotype, individual with different allelic pair (Dd) is said to have heterozygote genotype.

- The gene composition of one individual is the genotype of this individual.

1st Mendelian principle (law) : Genetic materials (gene) undergo segregation during gametogenesis and they are gathering (reunification) during fertilization (zygote formation).

A cross involving 2 characters together at once is called dihybrid cross.

A cross between 2 strains of peas yellow smooth seeds (GW) X green wrinkle seeds (gw)

G - dominant gene expressing yellow colour g - recessive gene expressing green colour

W - diminant gene expressing seeds with smooth surface w - recessive gene expressing seeds with wrinkle surface

P : Yellow smooth (♂) X green wrinkle (♀) GGWW ggww

gametes GW gw

F1 : GgWw (yellow smooth)

self fertilization GgWw X GgWw

F2 : GgWw (♂) X GgWw (♀) ♀ ♂

GW Gw gW gw

GW GGWWYellow smooth

GGWwYellow smooth

GgWWYellow smooth

GgWwYellow smooth

Gw GGWwYellow smooth

GGwwYellow wrinkle

GgWwYellow smooth

GgwwYellow wrinkle

gW GgWWYellow smooth

GgWwYellow smooth

ggWW Green smooth

ggWwGreen smooth

gw GgWwYellow smooth

GgwwYellow wrinkle

ggWwGreen smooth

ggww Green wrinkle

F2 genotype : (1 + 2 + 1) (1 + 2 + 1) : 1 + 2 + 1 + 2 + 4 + 2 + 1 + 2 + 1

F2 phenotype : (3 + 1) (3 + 1) 9 + 3 + 3 + 1

Exist as a result of random G, g, W and w gene segregation, leading to the formation of GW, Gw, gW and gw gametes either in ♂ or ♀ random combination to make up zygote.

2nd Mendelian principle (law) :

Each pair of different characters in hybrid union is independent of the other characters as that will be gamete formation with random combination of geneinvolved.

Mendelian law of random assortment of the genes.

Fork line diagram of dihybrid cross

GgWw X GgWw

(Gg X Gg) (Ww X Ww) 3 W- 9 G- W- (yellow smooth) 3 G- 1 ww 3 G- ww (yellow wrinkle)

3 W- 3 ggW- (green smooth)

1 gg 1 ww 1 ggww (green wrinkle)

Trihybrid cross involving three different genotypes

AaBbcc X aaBbCc

(Aa x aa) (Bb x Bb) (cc x Cc) 1cc 3A-B-cc 3B- 1C- 3A-B-C- 1A- 1bb 1cc 1A-bbcc

1C- 1A-bbC-

1cc 3aaB-cc 3B- 1C- 3aaB-C- 1aa 1bb 1cc 1aabbcc 1C- 1aabbC-

In monohybrid cross (involving 1 allele), ex. Aa 2 gemetes A and a are produced by gene segregation during gametogenesis after self fertilization, F2 individuals with 3 genotypes (AA, Aa, aa) and 2 phenotypes (A- and aa) are generated.

In dihybrid cross (2 alleles), ex. AaBb 4 gametes (AB, aB, Ab, ab) are produced through gene segregation during gameto-genesis after self fertilization, F2 individuals with 9 genotypes (AABB, AaBB, AABb, AaBb, AAbb, Aabb, aaBB, aaBb, aabb) and 4 phenotypes (A-B-, A-bb, aaB-, aabb) are generated.

The formulation of gametes, phenotypes, genotypes and phenotype proportions in crossing with different alleles

involvement

Crossing Gametes Phenotypes Genotypes Phenotype Proportion

Monohybrid 2 2 3 3 : 1

Dihybrid 4 4 9 9 : 3 : 3 : 1

Trihybrid 8 8 27 27 : 9 : 9 : 9 : 3 : 3 : 3 : 1

n 2n 2n 3n (3 : 1)n

Back cross and Test cross

Back cross is mating between individual genotype with one of the parent (P). P AA X aa

F1 Aa

back cross of Aa with AA produce one phenotype (A-) or two genotypes (AA and Aa) 1 : 1 Aa with aa produce two phenotypes (A- dan aa) or two genotypes (Aa and aa) 1 : 1

back cross is usually used for gene selection/purification in the purpose of gaining individuals carrying gene of interest. Application of back cross repeatedly allow separation (isolation) of one gene from a chromosome due to repeated crossing over during meiosis. Farming & animal husbandary : To gain lifestock with quality of interest.Medicine : To obtain animals of pure line for selected experimentation.

Test cross is mating between individual genotype with parent or other individual of recessive homozygote.

AA X aa Test cross between Aa and aa Aa X aa Aa Aa and aa 1 : 1test cross analysis allow detection of individual with unknown genotype.Heterozygote individual produce 2 phenotypes (A-) and aa.Homozygote individual produce 1 phenotype (A-) if it is dominant, or aa if it is recessive.

Modification (deviation) of Mendelian ratio

In some cases crossing between individuals may result in the modification or deviation of Mendelian ratio.

1. Semidominance (incomplete dominance)As dominant allele mask the expression of recessive allele incompletely,every genotype has a distinguishable phenotype. Heterozigouse genotypes express intermediate phenotype between dominant and recessive traits.ex. Dominant allele M of snapdragons (Merabilis jalapa) gives red flower.Recessive allele m gives white flower.Hetrozigous genotype Mm give rise the flower to pink as M allele is not completely dominant to m allele.Cross between 2 heterozygouse Mm produce F2 offsprings in the ratio red : pink : white = 1 : 2 : 1 (not 3 : 1).

2. CodominanceBoth alleles express traits independently to each other. In hetrozigous individual each allele is fully express, no dominancy of one allele to its partner or vice versa.Ex. ABO blood group IA allele expresses A antigen on the surface of erythrocytes. IB allele expresses B antigen on the surface of erythrocytes Individuals with AB (IA IB ) blood group express both A and B antigens on their erythrocyte surface.

AB X AB blood group IA IB IA IB

IA IA : IA IB : IB IB

A AB B 1 : 2 : 1

ABO blood group.

A and B group result from the peresence of different types of antigen (protein) on the erythrocyte surface determined by different alleles.

blood group genotype antigen A IA IA A B IB IB B AB IAIB AB O IO IO __ A IO IA A B IOIB B

3. Lethal genes (alleles)Alleles implicate with survival of individuals carrying this genes those carrying homozigous allele die & distorting Mendelian ratio.

Ex. Creeper hen have vestigial wings and legs. If two creeper hen are mated, there is a ratio of two creepers and one normal hen among their offsprings (not 3 : 1).

Creeper allele (C) is dominant in its effect on wings and legs length, but recessive on its effect on viability.CC lethal, die before hatchingCc creeper hencc normal hen, survive after hatching on

Human achondroplastic dwarfism are heterozygote (Xx) with short arms and legs.

If a couple with this condition marry (Xx X Xx), about one child in four dies before or soon after birth from a severe skeletal abnormality.XX dies from severe abnormal bone developmentXx viable but grow up shortxx survive without skeletal abnormality

4. Sex linked inheritance

Alleles (genes) which occupy loci within sex chromosomes, though express traits of non sex-determinersare said to be “sex linked”.

X linked inheritance recessive allele is transmitted from carrier mother to her son, or from a couple of carrier wife and affected husband to some of their daughters & all of their sons.

Ex. X linked hemophilia XnXh X XnY XnXh X XhY XhY XnXh XhXh XhY

Mendelian inheritance in human/medicine

Dominant inheritance – manifest inheritance whenever the gene is present, the effect is produced (manifested).

1. Anonychia — some or all of the nails of the fingers or toes are absent or rudimentary. Affected parent always inherits the discrepancy to some of his/her children.

2. Huntington disease gradual degeneration of nervous system develop to muscle paralysis & die in early/young age. Sufferer has at least one of his/her parent suffer this heritable disease.

3. Rhesus (Rh) factor

Rabbit immunized with erythrocyte of Macaca rhesus monkey anti Rh (Ab).

Rh(Ab) + Rh+ blood (Caucasian) agglutination Rh(Ab) + Rh- blood (non-Caucasian) no agglutination

Rh+ is dominant over Rh- Rh+ Rh+ X Rh-Rh- ↓ Rh+Rh- (haemolytic anemia / erythroblastosis fetalis)Rh+ child is always born by Rh+ parent, Rh- parent never give birth Rh+ child.

Recessive inheritance inheritance from both parents

1. Albinism — no pigment in the skin, hair & eyes combination of white hair, pink eyes and fair skin. Associated with serious defect of the eyes : nystagmus, error of refraction & photophobia.

The great majority of albinism are the offspring of parents who are normal in appearance.

2. Cystic fibrosis anomali/defect of exocrine gland - produce thick mucous - high concentration of NaCl in sweat - affect respiratory tract / lung prone to infection die in young age.

Normal parents may have cystic fibrosis children.Parents having child with cystic fibrosis, have the probability born another cystic child of ¼.

Aa X Aa ↓

Aa Aa Aa aa

Non-Mendelian genetics

Cytoplasmic inheritance

Mitochondria is an organell with its own DNA (is not interfeared by DNA genom). During fertilization sperm penetrate its head into the egg & leave the tail containing mitochondria outside.

zygote carry only mitochondria from egg (maternal) every individual mitochondrial DNA is inherited down the maternal line : from mother to children, and so on.

Ex : MELAS – Myoclonic Epilepsy Lactic acidosis and Stroke like episode. LOHN – Lebehr’s Hereditary Optic Neuropathy

Thank You for the Attention

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