Chromosomal Basis of Inheritance

1. Chromosomal Basis of Inheritance Genes reside on chromosomes. Sex Chromosomes and Autosomes Sex chromosomes contain genes that determine an organism’s sex (gender). The remaining chromosomes that are not directly involved in determining the sex of an individual are called autosomes.

2. Karyotypes: Male and Female

3. Chromosomal Inheritance • Sex Determination • In mammals, an individual carrying two X chromosomes is female. • An individual carrying an X and a Y chromosome is male. • Sex chromosomes pair during meiosis I. Meiosis proceeds, paired chromosomes separate = move to different cells. • Sperm has equal chance getting X or a Y chromosome • Egg only gets an X

4. Sex chromosomes • Male mammals, Y chromosome contains a gene called – SRY • Sex-determining Region Y • Codes for protein that causes the gonads of embryo to develop as testes. • Females don’t have SRY gene – develop ovaries

5. Effects of Gene Location • Sex-Linked Genes and Traits • Genes found on the X chromosome are X-linked genes. • A sex-linked trait is a trait whose allele is located on a sex chromosome. • Because males have only one X chromosome, a male who carries a recessive allele on the X chromosome will exhibit the sex-linked trait.

6. Gene location • Linked Genes • Pairs of genes that tend to be inherited together are called linked genes. • Chromosome Mapping • The farther apart two genes are located on a chromosome, the more likely a cross-over will occur. • Researchers use recombinant percentages to construct chromosome maps showing relative gene positions.

7. Genes on Chromosomes • Thomas Hunt Morgan • Provided convincing evidence that chromosomes are the location of Mendel’s heritable factors • Morgan worked with fruit flies • Because they breed at a high rate • A new generation can be bred every two weeks • They have only four pairs of chromosomes

8. Figure 15.3 • Morgan first observed and noted • Wild type, or normal, phenotypes that were common in the fly populations • Traits alternative to the wild type • Are called mutant phenotypes

9. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair • In one experiment Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) • The F1 generation all had red eyes • The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes

10. EXPERIMENT Morgan mated a wild-type (red-eyed) female with a mutant white-eyed male. The F1 offspring all had red eyes. P Generation X F1 Generation Morgan then bred an F1 red-eyed female to an F1 red-eyed male to produce the F2 generation. RESULTS The F2 generation showed a typical Mendelian 3:1 ratio of red eyes to white eyes. However, no females displayed the white-eye trait; they all had red eyes. Half the males had white eyes, and half had red eyes. F2 Generation Figure 15.4 • Morgan determined • That the white-eye mutant allele must be located on the X chromosome

11. CONCLUSION Since all F1 offspring had red eyes, the mutant white-eye trait (w) must be recessive to the wild-type red-eye trait (w+). Since the recessive trait—white eyes—was expressed only in males in the F2 generation, Morgan hypothesized that the eye-color gene is located on the X chromosome and that there is no corresponding locus on the Y chromosome, as diagrammed here. W+ W X X P Generation X X Y W+ W Ova (eggs) Sperm W+ W+ F1 Generation W+ W W+ Ova (eggs) Sperm F2 Generation W+ W+ W+ W+ W W W W+

12. Gene on Chromosomes • Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color trait • Was the first solid evidence indicating that a specific gene is associated with a specific chromosome • Genes on X chromosome X-linked genes • Genes on the Y chromosome Y-linked (SRY in humans) • Sex-linked

13. b+ vg+ bvg X Parents in testcross b vg b vg bvg b+ vg+ Most offspring or b vg b vg • Morgan determined that • Genes that are close together on the same chromosome are linked and do not assort independently • Unlinked genes are either on separate chromosomes of are far apart on the same chromosome and assort independently

14. XaY XAXA A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation. (a) Sperm Xa Y XAXa XAY Ova XA XAYa XAY XA (b)  If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder. XAXa XAY Sperm XA Y XAXA XAY Ova XA XaY XaYA Xa (c) If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.  XAXa XaY Sperm Xa Y Ova XAY XA XAXa Xa XaYa XaY Figure 15.10a–c • Sex-linked genes • Follow specific patterns of inheritance

15. Some recessive alleles found on the X chromosome in humans cause certain types of disorders • Color blindness • Duchenne muscular dystrophy • Hemophilia

16. Inheritance of Sex-Linked Genes • Muscular dystrophy • Absence of a key muscle protein – dystrophin • Gene locus on the X chromosome • Hemophilia • Sex-linked recessive disorder • Absence of one or more proteins used for clotting

17. X inactivation in Female Mammals • In mammalian females • One of the two X chromosomes in each cell is randomly inactivated during embryonic development • Barr body • Genes not expressed • In ovaries, Barr body chromosomes are reactivated to give rise to ova • Female gamete has an active X

18. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders • Large-scale chromosomal alterations • Often lead to spontaneous abortions or cause a variety of developmental disorders • Chromosome Mutations • Chromosome mutations are changes in the structure of a chromosome or the loss or gain of an entire chromosome. • Gene Mutations • Gene mutationsare changes in one or more of the nucleotides in a gene.

19. Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n  1 n + 1 n + 1 n –1 n + 1 n – 1 n n Number of chromosomes (a) (b) Nondisjunction of homologous chromosomes in meiosis I Nondisjunction of sister chromatids in meiosis II Figure 15.12a, b Abnormal Chromosome Number • When nondisjunction occurs • Pairs of homologous chromosomes do not separate normally during meiosis • Gametes contain two copies or no copies of a particular chromosome

20. Aneuploidy • Results from the fertilization of gametes in which nondisjunction occurred • Is a condition in which offspring have an abnormal number of a particular chromosome

21. If a zygote is trisomic • It has three copies of a particular chromosome • If a zygote is monosomic • It has only one copy of a particular chromosome

22. Alterations of Chromosome Structure • Breakage of a chromosome can lead to four types of changes in chromosome structure • Deletion • Duplication • Inversion • Translocation

23. A F H B C G C D F G B A E H E Deletion (a) A deletion removes a chromosomal segment. C E B C D A C D F G F H B A E H B G Duplication (b) A duplication repeats a segment. B A D A C D E F G H G C B E F H Inversion (c) An inversion reverses a segment within a chromosome. (d) A translocation moves a segment fromone chromosome to another, nonhomologous one. In a reciprocal   translocation, the most common type, nonhomologous chromosomes exchange fragments. Nonreciprocal translocations also occur, in which a chromosome transfers a fragment without receiving a fragment in return. A B M C D G E F G H N O C D E F H Reciprocal translocation M N A O P Q R B P Q R Figure 15.14a–d Alterations of chromosome structure

24. Human Disorders Due to Chromosomal Alterations • Alterations of chromosome number and structure • Are associated with a number of serious human disorders

25. Figure 15.15 Down Syndrome • Down syndrome • Is usually the result of an extra chromosome 21, trisomy 21

26. Aneuploidy of Sex Chromosomes • Nondisjunction of sex chromosomes • Produces a variety of aneuploid conditions • Klinefelter syndrome • Is the result of an extra chromosome in a male, producing XXY individuals • Turner syndrome • Is the result of monosomy X, producing an X0 karyotype

27. Genetics Problems • Pattern baldness is an example sex influenced trait that is dominant in males and recessive in females. A nonbald couple produced a bald son. What are the phenotypes of the parents? • Father is not bald – homozygous bb • Nonbald female can be Bb or bb • If son is bald then she must be Bb

28. Hemophilia is a recessive X-linked trait in humans. If a heterozygous woman has children with a normal man, what are the odds of the following combinations of children? • A) an affected son • B) an unaffected child • B) four unaffected offspring in a row

29. 1) Set up Punnett square • 2) ¼ • 3) ¾ • 4) 3/4x3/4x3/4x3/4 = 81/256

30. In humans, colorblindness (cc) is a recessive sex-linked trait. • Remember: XX - female XY - male

31. Two normal people have a colorblind son. • What are the genotypes of the parents? • XCX_? x XCY • What are the genotypes and phenotypes possible among their other children?

32. XC Y  parents XC XCXC XCY XcXCXcXcY 50%: female (one normal, one a carrier) 50%: male (one normal, one colorblind)

33. A couple has a colorblind daughter. • What are the possible genotypes and phenotypes of the parents and the daughter?

34. Xc Y XCXCXc XCY XcXcXcXcY parents: XcY and XCXcor XcXc father colorblind mother carrier or colorblind daughter: XcXc - colorblind

35. X-Linked Gene • Genes that are physically located on the X chromosome • Hemizygous • Used to describe single copy of an X-linked gene in the male

36. X-Linkage Recessive Trait • An affected male has a carrier mother • An affected female has a carrier or affected mother and an affected father • A carrier (female) has a carrier mother or an affected father

37. X-Linked Dominant Inheritance • X-linked conditions and traits are rare • Expressed in female in one copy • Has the associated trait/illness • High rate miscarriage rate for male babies • Affected female has an affected mother • Males have more severe effects • Passed from male to all daughters but to no sons

38. Problem • An unaffected woman who is heterozygous for the X-linked allele causing Duchenne muscular dystrophy has children with a normal man. What are the probabilities of the following? • An unaffected son • An unaffected son or daughter • A family of three children, all whom are affected

39. Hemophilia is a recessive X-linked trait in humans. If a heterozygous woman has children with a normal man, what are the odds of the following combinations of children? • An unaffected son • Four unaffected offspring in a row