Theme: Organism’s level of organization of hereditary information. Interaction of genes. Genetic linkage. Genetic of sex. Variation in human being as a.

Presentation on theme: "Theme: Organism’s level of organization of hereditary information. Interaction of genes. Genetic linkage. Genetic of sex. Variation in human being as a."— Presentation transcript:

1 Theme: Organism’s level of organization of hereditary information. Interaction of genes. Genetic linkage. Genetic of sex. Variation in human being as a quality of life and genetic phenomenon Lecturer: ass. prof. Tetyana Bihunyak

2 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

3 1. DNA 2. Gen 4. Genotype 5. Person 3. Chromosome 7. Population 6. Family (generation) Cell

4 Gregor Johann Mendel Austrian Monk, born in what is now Czech Republic in 1822 Son of peasant farmer, studied Theology and was ordained priest 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.

5 Mendel looked at seven traits or characteristics of pea plants

6 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 is present in the gametes

7 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:

8 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:

9 Gene – a unit of heredity; a section of DNA sequence encoding a single protein Genotype – 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

10 Genetics terms you need to know: diploid set of genes haploid set of genes 1234567 XX 8 9101112131415 171819202122 16 1234567 X 8 9101112131415 171819202122 16 GenotypeGenome

11 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:

12 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

13 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 F 1 = First filial generation; offspring from a genetic cross F 2 = Second filial generation of a genetic cross

14 1. The law of monotony of the first filial generation A - yellow seed; a - green seed P: ♀ AA x ♂ aa G (Gametes): A a F 1 : 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

15 2. The law of segregation A cross between plants obtained from F 1 plants. P: ♀ Aa x ♂ Aa G: A, a A, a F 2 : AA; Aa; Aa; aa From a pair of contrasting characters (alleles) only one is present in a single gamete and in F 2 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.

16 Getting all yellow seeds was an interesting result in itself Having viewed these results, Mendel then let the F 2 generation, was 6022 yellow seeds and 2001 green seeds. Two things stand out. green seeds disappeared in F 1, but come back in F 2. green seeds came back in F 2 as a specific proportion of the seeds as a whole.

17 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.

18 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: CCCcCc CcCc cc C c C c CC = normal Cc = carrier, no symptoms cc = has cystic fibrosis

19 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

20 Dihybrid cross: flower color and stem length TT PP  tt pp (tall, purple) (short, white) Possible Gametes for parents T P and t p F 1 Generation: All tall, purple flowers (Tt Pp) TtPpTtPpTtPpTtPp TtPpTtPpTtPpTtPp tp TP

21 Dihybrid cross F 2 If F 1 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 observed Tall, purple (9); Tall, white (3); Short, purple (3); Short white (1) TTPPTTPpTtPPTtPpTtPp TTPpTTppTtPpTtPpTtpp TtPPTtPpTtPpttPPttPp TtPpTtPpTtppttPpttpp TP Tp tP tp TP Tp tP tp

22 Genotype ratios (9): Four Phenotypes: 1 TTPP 2TTPp 2TtPP 4TtPp4TtPp 1TTpp 2Ttpp 1ttPP 2 ttPp 1ttpp Dihybrid cross: 9 genotypes Tall, purple (9) Tall, white (3) Short, purple (3) Short, white (1)

23 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

24 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

25 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  Genes show incomplete dominance when the heterozygous phenotype is intermediate.

26 Incomplete dominance Incomplete Dominance When F 1 generation (all pink flowers) is self pollinated, the F 2 generation is 1:2:1 red, pink, white R R r r R r R r

27 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 F 2 genotype and phenotype ratios are 1:2:1 GenotypePhenotype LMLMLMLM M LMLNLMLN MN LNLNLNLN N

28 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 –I A and I B alleles are dominant to the I O allele –I A and I B alleles are codominant to each other

29

30 Phenotype Possible Genotype Antigen on RBC surface Antibody Made in Plasma AI A I O, I A I A AAnti-B BI B I O,I B I B BAnti-A ABIAIBIAIB Neither OIOIOIOIO OBoth

31 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.

32 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.

33 Skin color is quantitative trait, that are controlled by two pairs of genes A 1 a 1, A 2 a 2. Let’s sign skin color as A 1 A 1 A 2 A 2 – very dark A 1 A 1 A 2 a 2 or A 1 a 1 A 2 A 2 — dark A 1 a 1 A 2 a 2 — medium brown A 1 a 1 a 2 a 2 or a 1 a 1 A 2 a 2 — light a 1 a 1 a 2 a 2 — white (pale skin).

34 TASK A woman with white skin married a medium-brown man. What is the skin color possible for their children? P: ♀ a 1 a 1 a 2 a 2  ♂ A 1 a 1 A 2 a 2 G: a 1 a 2 A 1 A 2, A 1 a 2, a 1 A 2, a 1 a 2 F1: A 1 a 1 A 2 a 2 ; A 1 a 1 a 2 a 2 ; a 1 a 1 A 2 a 2 ; a 1 a 1 a 2 a 2

35 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.

36 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

37 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. _____ I A and I B alleles are codominant to each other 5. _____A single pleiotropic gene can affect several traits

38 Gene is a small segment of DNA that codes the synthesis of a specific protein. Genes are located on the chromosomes. In human karyotype there are 46 chromosomes. In human diploid number there are thousands of different genes. Many genes may be present on the same chromosome. Such genes are said to be linked, or to constitute a linkage group. Linked genes were discovered by great American geneticist Thomas Hunt Morgan of Columbia University in 1910.

39 Unlinked Genes

40 Linked Genes

41 Thomas Hunt Morgan (1866-1945) Nobel prize in 1933 for his research on the fly Drosophila in linkage and crossing-over, which he used to map the linear arrangement of genes along the chromosome.

42 T. H. Morgan studied chromosomes of Drosophila melanogaster (fruit-fly) The fruit-fly was selected because 1) it breeds rapidly, attaining maturity in twelve days; 2) 30 generations can be bred in one year; 3) it has only eight chromosomes.

43 L = long wings l = short wings G = gray body g = black body

44 Autosomal Linkage. Dihybrid Testcross

45 F 2 : 41.5% 8.5% 41.5%

46 Distance between the linked genes is measured in centimorgans (cM) or map units. 1 cM = 1 map unit = 1% of crossing over = 1% crossover gametes = 1% recombinants

47 Linkage between genes on the same chromosome 1) complete linkage - when genes stay together at a very short distance on the chromosome; person with complete linked genes can form only noncrossover gametes. 2) incomplete linkage - when genes stay together at a far apart (under 50 cM); person with incomplete linked genes can produce crossover and noncrossover gametes, because during meiosis crossing-over takes place.

48 Chromosome theory of linkage: 1) Genes lie in a linear order on the chromosomes. The position of a gene on a chromosome is locus. 2) Genes located on the same chromosome are linked or constitute a linkage group. The number of linkage groups is exactly the number of chromosome pairs in the organism. 3) Linkage between two genes can be interrupted by crossing-over (alleles exchanges between homologous chromosomes during meiosis). 4) The distance between the linked genes on the chromosome determines the strength of linkage. Linkage strength between two genes turn out to the distance between them.

49 Sex determination in humans P: 44 A + XX  44A + XY Gametes: 22A + X 22A + X; 22A + Y F 1 : 44 A + XX; 44A + XY. In human being sex inherits as Mendelian Trait. The sex of the offspring is determined by the kind of sperm that will fertilize an egg. If fertilization is by an X-bearing sperm, the resulting zygote will be XX and will develop into a female. If fertilization is by a Y-bearing sperm, the resulting zygote will be XY and will develop into male.

50 Sex determination in humans

51 Sex differentiation in humans takes place during embryonic development. Gene Sry (for sex determining region of the Y chromosome) that directs development of gonad to testis and secreting of androgens is presence on the short arm of the Y- chromosome. If it is absence, the gonad becomes an ovary and female structures (uterus, Fallopian tubes) develop.

52 Variation is deviation in characters in an individual from those typical of the species to which it belongs. Variation of organisms is subdivided into: 1) non-hereditary (phenotypic or modification) and 2) hereditary (genetic variation).

53 Phenotypic (modification) variation are changes of phenotype without changes of the genotype, these changes are adaptive reactions to external stimuli and they do not inherit. Hereditary (genetic variation) is subdivided into: 1) combinatorial variation and 2) mutation.

54 Combinatorial variation is formation of new combinations of genotypes by shuffling of parental genes. New genotypes arise in 3 ways: 1) recombination of linked genes in chromosomes by crossing over in the prophase of meiosis; 2) independent assortment of chromosomes during meiosis; 3) random combination of chromosomes during fertilization. As a result of combinatorial variation is deviation in characters of the offspring from those of its parents.

55 Crossing-over

56 Mutation is a permanent transmissible change in the genetic material (modification in chromosomes and genes). There are 3 main types of mutations: 1) chromosome mutations (genomic mutation) are changes in number of chromosomes in karyotype; 2) chromosome aberrations are changes in structure of chromosomes; 3) gene (point) mutations are changes in structure of the nucleotides.

57 Сhromosome mutations are subdivided into: 1)polyploidy is the state of having more than diploid set of chromosomes: 3n (triploid), 4n (tetraploid), 5n (pentaploid), 6n (hexaploid); 2) aneuploidy is any deviation of the diploid number of chromosomes, an individual or cell having a missing (2n-1) or extra (2n+1) chromosomes.

58 Human Trisomy 21 XY male (47,XY,21+)

59 Duplication - a segment of a chromosome joins a part of homologous chromosome

60 Inversion - a segment of a chromosome breaks off and rotates through 180º and rejoining the chromosome

61 Translocation - a segment of a chromosome breaks off and joins a non- homologous chromosome

62 A good example is the translocation between chromosomes 9 and 22, creating the “Philadelphia chromosome” This causes about 90% of the cases of chronic myelogenous leukemia

63 A gene mutation or point mutation (since it applies to a particular gene locus) is the result of a change in the nucleotide sequence of the DNA molecule in a particular region of the chromosome

64 Such a change in the base sequence of the gene is transmitted to mRNA during transcription and may result in a change in the amino acid sequence of the polypeptide chain produced from it during translation at the ribosomes

65 Gene mutations

66 Gene mutations occurring during gamete formation are transmitted to all the cells of the offspring and may be significant for the future of the species. Somatic gene mutations which arise in the organism are inherited only by those cells derived from the mutant cells by mitosis.

67 Sickle cell anaemia in humans is an example of base substitution mutation affecting a base in one of the genes involved in the production of haemoglobin

68 Hemoglobin and Sickle Cell Anemia Single base mutation in DNA –A to T transversion Single amino acid change in the protein –Glutamine to Valine NH 2 C H O CH 2 CH 2 O NH 2 OH Glutamine NH 2 C H C H CH 3 O CH 3 OH Valine

69 Sickling Cells Polymers of hemoglobin deform red blood cells Normal Sickle

70 Sickle Cell Anemia Recessive trait Symptoms: –Chronic hemolytic anemia –Severe pain –Rapid septicemia (infection) –Asplenia (no spleen left)

71 How Was the Mutation Selected? Malaria –Mosquito born plasmodium parasite –Some sickling is good Heterozygotes have the advantage!

72 “He who likes to eat fruit must climb the tree” (English proverb)