Principles of heredity, Mendelian laws Marie Černá Lecture No 403-Heredity

1865 – Gregor Mendel

Mendel’s experiments Pisum sativum pod/flower location 7 characters described in work „Experiments with plant hybrids“.

Terms character (gene) – a heritable feature (flower color) trait (allele) – each variant for a character (purple or white for flower color) hybrid - the result of breeding (hybridization) P generation (parental generation) F 1 generation (first filial generation) F 2 generation (second filial generation) B 1 backcross (F 1 x parent) Testcross (PP or Pp x pp) monohybrid cross - only one character is studied dihybrid cross - two characters are studied simultaneously

Relation of alleles in a heterozygote dominance – manifestation of both AA and Aa genotypes dominant allele masks the expression of recessive allele in heterozygote recessivity – manifestation of aa genotype only

incomplete dominance heterozygote’s phenotype is intermediate between that of both homozygotes (dominant and recessive)

Dominant / recessive alleles at the level of a) all organism – complete dominance b) biochemical – incomplete dominance c) molecular – codominance Round seed shape Low osmotic pressure (no water absorption into seeds) Enzyme for metabolism sugar into starch Wrinkled seed shape High osmotic pressure (water absorption that is then lost) Defective form of enzyme

HOMOZYGOTE – two identical alleles at a given locus on a pair of homologous chromosomes => 1 type of gametes HETEROZYGOTE – two different alleles at a given locus on a pair of homologous chromosomes => 2 different gametes A A A A A A a a meiosa meiosa

Gametes P(A)=P(a)=1/2 AA x aa Aa aa AA Aa A a A A a a P F1 F2 parental generation homozygotes (dominant and recessive) the 1st filial generation heterozygote the 2nd filial generation genotypes of zygotes Monohybrid cross Monohybrid = crosser that is different in 1 allelic pair (gene) Genotypes of gametes

AAAaaa A-aa :: : AAAa aa AA Aa aa the 2nd filial generation genotype ratio: 1 : 2 : 1 phenotype ratio: 3 : 1 B 1 backcross – verification of hybrid’s heterozygosity (F1 x parent) Testcross (F1 x recessive homozygote) xx ratio 1 : 1

Dihybrid cross 2 allelic pairs (genes) carried by different pairs of homologous chromosomes – segregate independently two types of parental crosses P: AABB x aabb AAbb x aaBB F1: AaBbdouble heterozygote genotypes of gametes: AB Ab aB ab 1 : 1 : 1 : 1

F2 ABAbaBab AB AABBAABbAaBBAaBb Ab AABbAAbbAaBbAabb aB AaBBAaBbaaBBaaBb ab AaBbAabbaaBbaabb Genotypes of gametes Punnett square:

F2 Genotypes: AABB AABb AAbb AaBB AaBb Aabb aaBB aaBb aabb 1 : 2 : 1 : 2 : 4 : 2 : 1 : 2 : 1 = (1 : 2 : 1)(1 : 2 : 1) Phenotypes: A-B- A-bb aaB- aabb 9 : 3 : 3 : 1 = (3 : 1)(3 : 1) Breeding news = homozygotic recombined forms = new combinations of parental properties For parental cross:AABB x aabb → AAbb, aaBB AAbb x aaBB → AABB, aabb

B1 backcross - testcross AaBb x aabb heterozygote x recessive homozygote ABAbaBab AaBbAabbaaBbaabb 1 : 1 : 1 : 1

Trihybrid cross 3 allelic pairs (genes) four types of parental crosses P: 1) AABBCC x aabbcc 2) AABBcc x aabbCC 3) AAbbcc x aaBBCC 4) AAbbCC x aaBBcc F1: AaBbCc 8 types of gamets: ABC ABc AbC Abc aBC aBc abC abc 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 F2: 64 of zygotic combinations

Calculations of ratios: by combinatory square (Punnett square) by combination of monohybrid ratios (1AA:2Aa:1aa)(1BB:2Bb:1bb)(1CC:2Cc:1cc) by the calculation of probabilities

Polyhybrid cross n – number of followed traits number of gametes 2 n number of zygotes 4 n genotype ratio: ( 1 : 2 : 1 ) n phenotype ratio: ( 3 : 1 ) n

1. Uniformity of F1 generation identity of reciprocal crosses During formation of gametes: 2. Principle of segregation two alleles of one gene separate from each other into two gametes 3. Principle of combination - independent assortment alleles of two or more allelic pairs (genes) assort independently of one another there are as many types of gametes as possible random combinations of paternal and maternal chromosomes (genes on different chromosomes behave independently) MENDEL’S LAWS

Lethality, decreased vitality Decreased penetrance Different expressivity Sex linked heredity Gene linkage Gene interactions Polygenic heredity Mitochondrial heredity Gene imprinting (transcription only of one allele) Dynamic mutations (amplification of triplet repeats) Structural balance chromosomal aberrations Differences from the Mendel’s laws

Lethality, decreased vitality all genotypes are not vital in the same way - zygote dying or individuals do not live to fertility - change of ratios COMPLETE RECESSIVE LETHALITY Lethal is a homozygote (dominant or recessive) 0 AA : 2 Aa : 1 aa or 1 AA : 2 Aa : 0 aa Ex. In mice: A – yellow coat, a – black coat AA = lethal, yellow mice only Aa Allele A – 2 expressions (pleiotropy) - dominant = yellow coat - recessive = premature embryo dying COMPLETE DOMINANT LETHALITY Lethal is a dominant homozygote and a heterozygote 0 AA : 0 Aa : 1aa It forms by new mutation and is not transmitted.

COMPLETE RECESSIVE LETHALITY gametes zygotes adult individuals

Decreased vitality - recessive 1 AA : 2 Aa : 1 aa - dominant 1 AA : 2 Aa : 1 aa

Thomas Hunt Morgan

Mendel´s 3rd law only applies to allelic pairs (genes) carrying on different pairs of homologous chromosomes (independent assortment) Genes on 1 chromosome – are not assorted independently - are linked, transmitted together into gametes Genes on 1 chromosome = linkage group Strength of linkage depends on their distance: More are farther from each other – higher probability of crossing over

Morgan’s laws Genes on chromosome are in linear order No of linkage groups is equal to No of homologous chromosomes pairs Gametes with assortment of linked alleles, that is different from parental one, form only in the case of recombination (crossing over) Frequency of these recombinations sets strength of linkage

1944 – Avery, MacLeod, McCarty the demonstration of DNA as genetic material

Role of genetics in medicine Universal validity of Mendel´s laws 1902 Garrod: the first human disease with Mendelian heredity - alkaptonuria (disorder of metabolism of amino acids - phenylalanine and tyrosine) Use in medical practice: genetic counselling –calculation of probability in monogenic and polygenic disorders

ABO blood groups

Frequencies (%) of blood group system in the U.S.A. population Blood group Blood antigen Antibody in serum White Caucasians BlacksAsians American Indians OHanti-A,B AAanti-B BBanti-A AB -4451

Rh blood group

Blood group donors and recipients

Literature Biology, eighth edition, Neil A. Campbell, Jane B. Reece Pearson International Edition, 2008 Unit three: Genetics Chapter 14: Mendel and the Gene Idea Chapter 15: The Chromosomal Basis of Inheritance pages 262 – 304