Sex-linked

1. As you all know genes reside on chromosomes. This basic fact is called the chromosome theory of inheritance. However earlier in this century, the issue of where the units of heredity resided was fiercely debated. The notion the genes were located on the chromosomes came from the recognition that the behavior of Mendel's particles during meiosis parallels the behavior of chromosomes at meiosis. Mendel’s Laws of independent assortment imply that genes on the same chromosome are inherited together and genes on different chromosomes are inherited independently.

2. Sex-linked Although these were convincing correlations, actual proof of the chromosome theory required the discovery of sex linkage. Remember, Mendel had found that reciprocal crosses produce equal results with respect to the progeny. In general geneticists confirmed his results. However exceptions did arise. The most famous exception was that discovered by Tomas Hunt Morgan in the fruit fly Drosophila melanogaster. Drosophila eyes are normally bright red. Morgan discovered an exceptional white-eyed male. He performed the following crosses:

3. Morgans crosses

4. X and Y chromosomes Somehow eye color was linked to sex  The key to understanding this pattern of inheritance arose from work demonstrating that males and females of a given species often differ in the chromosome constitution. For example, they found that male and female Drosophila both have four chromosome pairs. However in males one of the pairs the members differed in size: Female Drosophila: Male Drosophila:

5. Sex chromosomes 2 : 2 Morgan realized that difference in chromosome constitution was the basis of sex determination in Drosophila: Females produce only X-bearing gametes, while males produce X and Y-bearing gametes. If the gene for eye color resides on a X chromosome There is no counterpart for this gene on the Y chromosome

6. Formal explanation white XwY Red XWXW Females have 2 copies of the eye color gene males have one copy W (red) is dominant over w (white) F1

7. Formal explanation Red XWY Red XWXw Females have 2 copies of the eye color gene and males have one copy W (red) is dominant over w (white) F2

8. Formal explanation Red XWY White XwXw The reciprocal cross F1 In the F1 all the females are red and all the males are white

9. Formal explanation White XwY Red XWXw F2

10. This explanation also accounts for the fact that equal numbers of male and female progeny are produced. With this explanation of sex determination, Morgan realized that he could explain the inheritance patterns of eye color by assuming: The gene determining eye color resides on the X chromosome (red and white eyes represent normal and mutant alleles of this gene) 2. There is no counterpart for this gene on the Y chromosome Thus females carry two copies of the gene, while males carry only a single copy.

11. Red-green color blindness Red-green color blindness means that a person cannot distinguish shades of red and green. Males are affected 16 times more often than females, because the gene is located on the X chromosome. In color-blind men, the green or red cones worked improperly. The genes for the red and green receptors were altered in these men X-linked red-color blindness is a recessive trait. Females heterozygous for this trait have normal vision. The color perception defect manifests itself in females only when it is inherited from both parents. By contrast, males inherit their single X-chromosome from their mothers and become red green color blind if this X-chromosome has the color perception defect. The dominant (normal) X chromosome is represented as XCB. The recessive (mutant) chromosome is represented as Xcb. Since males have only one X-chromosome, if this chromosome has the red-green color blind allele, the males will have the color perception defect. Females have 2 X-chromosomes. Both X-chromosomes must carry the mutant allele for the females to be color blind. Red-green color blind females are homozygous for the recessive allele. Females with one mutant allele and one normal allele are heterozygous "carriers". They are not color blind, but they can pass the color blindness to their children.

12. Sex determination • Bridges a student of Morgan set up the cross outlined above in • large numbers • P cross: • white females x red males • XwXw x XWY • As expected, he obtained red-eyed females (XwXW) and white-eyed males (XwY)

13. Primary exception • About 1 in every 2000 progeny he obtained a white-eyed fertile female or a red-eyed sterile male. • These were called primary exceptional progeny • How can these exceptional progeny be explained? • Bridges suggested that occasionally during meiosis the X chromosomes fail to separate during meiotic division. • ｷNormal separation of the X chromosomes • produces Xw gametes • ｷFailure of X chromosome separation • (non disjunction) XwXw and nullo gametes autosome autosome X X Non-disjunction disjunction

14. Bridges and non-dysjunction white XwXw red XWY F1

15. Bridges assumed that XXX and Y0 progeny die and the only two viable progeny types were XXY and X0 In this model sex is determined by the number of X chromosomes rather than the presence or absence of the Y chromosome This model makes a strong prediction that is genes reside on chromosome the exceptional red-eyed males should be X0 and the exceptional white eyed females should be XXY. THAT IS WHAT BRIDGES FOUND (something to think about: What classes of progeny would be expected from the cross XwXwY x XWY ?)

16. Sex chromosomes and sex Species XX XY XXY XO Drosophila female male female male Humans female male male female In Drosophila, it is the number of X's that determine sex. In mammals it is the presence or absence of a Y chromosome that determines sex.

17. Bridges and Triploids XW Y XWY Red male YY lethal Y XW XwXw lethal XwXw Y XwXw white female XW Xw Red female Xw Y Xw White male XW XwY Red female XwY Y XwY White male White XwXwY red XWY

18. Triploidy Species that are triploid, reproduce asexually (plant species) What are the consequences of triploidy during mitosis and meiosis? Diploid Haploid Triploid Mitosis

19. Triploidy Species that are triploid, reproduce asexually (plant species) What are the consequences of triploidy during mitosis and meiosis? Diploid Haploid Triploid Mitosis

20. Meiosis and triploids MeiosisI This is for one chromosome. If there are n chromosomes in an organism, then balanced gametes (equal copies of all chromosomes) are very rare.

21. Meiosis and triploids Triploids produce unbalanced gametes 4N 3N 3N 2N MeiosisI This is for one chromosome. If there are n chromosomes in an organism, then balanced gametes (equal copies of all chromosomes) is very rare.

22. Seedless watermelons Triploidy is useful in agriculture. Biological control: Cross a tetraploid watermelon with a diploid watermelon

23. And triploid toads Triploid toads Nature Genetics 30, 325 - 328 (2002) Tetraploid green toads reproduce through diploid eggs and sperm cells. A new taxon was discovered at an isolated site in the Karakoram mountain range. Every wild toad caught from eight localities was triploid Did not find a single diploid or tetraploid Batura toad. Both males and females were found 3N female 3N male N elimination N elimination 2N 2N 2N N N 3N

24. Sex in organisms Species XX XY XXY XO Drosophila female male female Male (sterile) Humans female male male female Sex chromosomes and sex linkage: In Drosophila, it is the number of X's that determine sex while in mammals it is the presence or absence of a Y chromosome that determines sex. Homogametic sex- Producing gametes that contain one type of chromosome (females in mammals and insects, males in birds and reptiles) Heterogametic sex- Producing gametes that contain two types of chromosomes (males in mammals and insects, females in birds and reptiles) Bridges could tell genotype by where the sex chromosome went and therefore established that chromosomes carried genes

25. Non-sex chromosomes are called autosomes Humans have 22 autosomes, Drosophila has 3 Homogametic sex- XX- females in humans males in birds Heterogametic sex- XY- males in humans Hemizygous gene present in one copy in a diploid organism Human males are hemizygous for genes on the X-chromosome

26. Sex linked Described below is an actual case history of the use of pedigree analysis: After the death of a wealthy individual (II:3), a man claiming to be his son (III:3) filed a paternity suit and claimed the inheritance. The deceased had only two living nephews (III:1 and III:2 who were sons of his brothers (II:1 and II:2). In determining whether the man was actually the son and had the rights to the inheritance which of the following markers would be most useful Autosomal X-linked Y-linked $$$

27. Surname project Y Y Y Y All males in this pedigree will have the SAME Y-chromosome!!!

28. Mendelian genetics in Humans: Autosomal and Sex-linked patterns of inheritance Obviously examining inheritance patterns in humans is much more difficult than in Drosophila because defined crosses cannot be constructed. In addition humans produce at most a few offspring rather than the hundreds produced in experimental genetic organisms such as Drosophila It is important to study mendellian inheritance in humans because of the practical relevance and availability of sophisticated phenotypic analyses. Therefore the basic methods of human genetics are observational rather than experimental and require the analysis of matings that have already taken place rather than the design and execution of crosses to directly test a hypothesis To understand inheritance patterns in human genetics you often follow a trait for several generations to infer its mode of inheritance. For this purpose the geneticist constructs family trees or pedigrees. Pedigrees trace the inheritance pattern of a particular trait through many generations. Pedigrees enable geneticists to determine whether a familial trait is genetically determined and its mode of inheritance (dominant/recessive, autosomal/sex-linked)

29. Pedigree symbols: Male Female Sex Unknown 5 Affected individual Deceased Number of individuals Spontaneous abortion Termination of pregnancy

30. Pedigree symbols: relationship line Sibship line line of descent individual’s lines consanguinity Monozygotic Dizygotic

31. Characteristics of an autosomal recesssive trait: Patterns in pedigrees of Autosomal recessive traits: There are several features in a pedigree that suggest a recessive pattern of inheritance: Rare traits, the pedigree usually involves mating between two unaffected heterozygotes with the production of one or more homozygous offspring. 2. The probability of an affected child from a mating of two heterozygotes is 25% 3. Two affected individuals usually produce offspring all of whom are affected 4. Males and females are at equal risk, since the trait is autosomal 5. In pedigrees involving rare traits, consanguinity is often involved. In the pedigree shown below, an autosomal recessive inheritance pattern is observed:

32. Characteristics of an autosomal dominant trait: 1. Every affected individual should have at least one affected parent. 2. An affected individual has a 50% chance of transmitting the trait 3. Males and females should be affected with equal frequency 4. Two affected individuals may have unaffected children

33. The following pedigree outlines the typical inheritance pattern found in red-green color-blindness. Does this fit an autosomal recessive or autosomal dominant pattern of inheritance?

34. Characteristics of a sex-linked trait: Hemizygous males and homozygous females are affected Phenotypic expression is much more common in males than in females, and in the case of rare alleles, males are almost exclusively affected Affected males transmit the gene to all daughters but not to any sons Daughters of affected males will usually be heterozygous and therefore unaffected. Sons of heterozygous females have a 50% chance of receiving the recessive gene.