Chromosome Number and Structure: Influence on Genetic Variation and Abnormalities

1. Week 11 CHROMOSOMES Chapter 10 pages 180-186 Genetics I Chapter 11 pages 189-201

2. HOMEWORK Chapter 10 pages 180-186 Chapter 11 pages 190 - 207

3. CHROMOSOME NUMBER AND STRUCTURE Crossing over of chromosomes creates variation within a population during meiosis Proper separation of chromosomes during meiosis is critical for proper growth and function Improper separation of chromosomes results in abnormal chromosome numbers in individuals due to: • Nondisjunction= When chromosomes fail to properly separate during meiosis • Errors in crossing-over which result in extra or missing parts of chromosomes

4. Crossing Over NonDisjuction

5. Aneuploidy Euploidy= Correct number of chromosomes in a species Aneuploidy= A change in the number of chromosomes due to nondisjuction

6. Monosomy and Trisomy Monosomy and Trisomy are two different states of Aneuploidy (change in x-some # due to nondisjunction) Monosomy- an individual has only 1 copy of a chromosome (2n-1) Trisomy- an individual has 3 copies of a chromosome (2n+1)

7. Monosomy Example Females normally have two X chromosomes Lack of one of the X x-somes results in: Turner Syndrome (Monosomy X) Only 1 copy of the X chromosome

8. Trisomy Example Down Syndrome Extra copy of chromosome at location 21 (Trisomy 21) Pheontype:

9. Types of Nondisjuction PrimaryNondisjunction - Occurs during meiosis I - Both homologous chromosomes go into the same daughter cell SecondaryNondisjunction - Occurs during meiosis II - Sister chromatids fail to separate and both chromosomes go into the same gamete

10. Page 180 Figure 10.10 Secondary Nondisjunction Results in 2 normal and 2 aneuploid gametes Primary Nondisjunction No normal gametes produced!!

11. Three non-lethal Trisomic Conditions Trisomy 13 Patau’s Syndrome Trisomy 18 Edwards Syndrome Trisomy 21 (only type of aneuploidy where able to survive beyond early childhood)

12. Autosomes v. Sex Chromosomes Autosomes - All non sex chromosomes Sex Chromosomes - The X or Y chromosomes - Females have two copies of the X chromosome - Males have one copy of the X chromosome and one copy of the Y chromosome

13. Sex Chromosome Aneuploidy Change in sex chromosome number Occurs via nondisjunction during spermatogenesis or oogenesis Results in an abnormal number of chromosomes in the gametes These abnormalities are better tolerated than autosomal anueploidy conditions like Trisomy

14. Normal v. Abnormal Sex x-some Karyotypes NORMAL Karyotype ABNORMAL Karyotype

15. Only 1 X x-some = Female with Turner Syndrome (sterile) Two X and 1 Y x-somes = Male with Klinefelter Syndrome (sterile)

16. Swyer Syndrome Swyer Syndrome (“hermaphrodite”) • Deletion of the SRY gene on the Y x-some • Result is an “XY Female” • Lack hormone called ‘Testis-determining factor’ • Male genitals are not fully developed  female designation Caster Semenya won gold at world Championships in 800m race *Almost stripped of medal due to her XY Female status (she has no womb/ovaries but has internal testes)

17. de la Chapelle Syndrome de la Chapelle Syndrome • Movement of the SRY gene from the Y x-some to an X chromosome • Results in a “XX Male” • Men have undersized testes, sterility and slight breast development • The SRY gene determines “maleness” NOT the number of X chromosomes b/c without the SRY gene, a person will be female

18. Why are extra sex chromosomes better tolerated than extra autosomal chromosomes? Males and females produce equal amounts of gene product eventhough females have 2 X chromosomes Only one of the X x-somes is functional If a person has > 1 X x-some, the others are inactive and are known as BARR BODIES Therefore, gene dosage is the same whereas in autosomes, extra copies leads to unequal gene dosage

19. TURNER SYNDROME (XO) Only 1 Sex Chromosome (X) Incidence= 1 in 10,000 females (.01%) Phenotype Widely spaced nipples Low posterior hairline Neck webbing Ovaries, oviducts and uterus are underdeveloped Do not undergo puberty or menstruate Breasts do not develop Normal intelligence “Normal” lives if take hormone supplements

20. KLINEFELTER SYNDROME Male with Klinefelter has 2 or more X x-somes in and 1 Y x-some Extra X x-some becomes a Barr Body Incidence is 1 in 500 to 1,000 males (.1-.2%) Phenotypes Underdeveloped prostate gland and testes No facial hair Some breast development Large hands and feet Long arms and legs Sterile Risk of breast cancer, osteoporosis and lupus (normally affect females) Testosterone therapy is a solution

21. Poly-X FEMALES Often called, “Superfemales” Have > 2 X x-somes Females with 3 X x-somes tend to be tall and thin Incidence is 1 in 1,500 females (.07%) XXXX females are very tall and severly mentally retarded

22. JACOBS SYNDROME X Y Y Males “Supermales” Due to nondisjunction during spermatogenesis Frequency of karyotype is 1/1,000 (.1%) Males are taller than average, have persistent acne, speech and reading issues, are fertile

23. CHANGES IN CHROMOSOME STRUCTURE Changes in chromosome structures are mutations X-somes can break due to radiation, organic chemicals and viruses End of chromosomes break and can go back together improperly which leads to chromosomal mutations: Deletions Duplications Translocations Inversions

25. Deletions • Occur when: • 1. The end of a x-some breaks off • When two simultaneous breaks lead to the loss of an • Internal segment • Deletions can lead to abnormalities

26. Duplications • Occur when: • A chromosomal segment is present more than once in • the same chromosome • Duplications may or may not cause visible abnormalities • (depends on size of the duplicated region)

27. Inversions • Occur when: • A chromosomal segment is turned 180 degrees • Inversions usually do not cause visible abnormalities • However, reversed gene sequences can cause • duplications or deletions in offspring

28. Translocations • Occur when: • A chromosome segment moves from one chromosome to • a non-homologous chromosome • Translocations can be: • Balanced (as shown on left)- A reciprocal swap • 2. Unbalanced- extra material from on x-some and missing • material from another (occurs when people with translocations • have offspring) • Unbalanced translocations can lead to miscarriage or if • the fetus survives, the child will have severe symptoms • Down syndrome can also be caused by a translocation btwn. • X-somes 21 and 14

29. Human Syndromes Are discovered when observing karyotypes of various syndromes Can be understood by looking at patterns of inheritance in families

30. Deletion Syndromes Williams Syndrome - Chromosome 7 loses a small piece of the end Phenotype Broad forehead Low nasal bridge Anteverted (upturned) nostrils Full cheeks Wide mouths Small chin Large ears Musical and verbal abilities are unaffected

31. Deletion Syndromes Cri du chat (Cat’s Cry) syndrome -Chromosome 5 is missing a piece of the end Phenotype Smaller head Mentally retarded Facial abnormalities Abnormal development of the glottis and larynx  infant’s cry is reminiscent of a cat A= 8 mo. B= 2 yrs. C= 4 yrs. D= 9 yrs.

32. Translocation Syndromes If the translocation is balanced, no abnormal phenotypes If the translocation breaks an allele into two, health problems arise Ex. Translocation between x-some 2 and 20 leads to eye and internal organ abnormalities and severe itching (the translocation disrupts the alleles on x-some 20)

33. Cancer and Translocations Translocations can induce certain cancers Ex. Translocation of x-some 22 into x-some 9 can cause chronic myelogenous leukemia = “The Philadelphia Chromosome” Ex. Burkitt Lymphoma- from x-some 8 to 14, large tumors in jaws (common in children from equatorial Africa)

34. Summary X-some STRUCTURE changes Deletions Duplications Inversions Translocations X-some NUMBER changes Autosomal Monosomy Trisomy Sex x-some XO XY Female XXY XX Male

35. QUESTIONS??