Chromosomal Abnormalities I SDK October 13, 2012

1. Chromosomal Abnormalities ISDKOctober 13, 2012

3. Chromosomal Abnormalities What are chromosome abnormalities? A chromosome abnormality reflects an abnormality of chromosome number or structure. We can classify them into: I- NUMERICAL ABNORMALITIES II- STRUCTURAL ABNORMALITIES

4. Characteristics of Chromosomal Abnormalities • The majority of human chromosomal abnormalities occur in the Autosomes.  • Most of these abnormalities are monosomies or trisomies.  • In the case of a monosomy, there is only one copy of each kind of chromosome instead of the usual pair of homologous chromosomes.  • With trisomy, there are three of each type of chromosome.  • All fetuses with autosomal monosomies spontaneously abort early in pregnancy.  • Likewise, almost all fetuses with trisomies die before birth.  • Those that survive usually have multiple physical malformations, mental retardation, and relatively short lives.

5. I. NUMERICAL ABNORMALITIES

6. NUMERICAL ABNORMALITIESHOW DOES IT HAPPEN Chromosomal abnormalities in the number of chormosomes. 1.Euploidy: Cells has chromosomes multiple of 23 such as • 23, 46. 69, and 92 • These may be normal or Abnormal • Normal • Haploid cells : Gametes has 1 copy each 23 cells • Diploid cells: Somatic cells has 2 copy each 23 x2 46 Abnormal • Tripoloidy 3 copies of each chromosome 23 x 3= 69 • 1 egg fertilized by 2 sperms • Tetra ploidy. 4 copies of each chromosome 23 x 4= 69 • 1 egg fertilized by 3 sperms

7. 2.Aneuploidy • Deviation from normal number of chromosomes due to loss or gain of specific chromosomes. • Generally caused by non disjunction of chromosome during meiosis. • is one extra (trisomy ; 2n + 1 ) or • one less chromosome (monosomy;2n - 1). • It is a major cause of human reproductive failure. • Most human miscarriages are aneuploids. • All autosomal monosomies are lethel • All Trisomiesare also lethel • But some Trisomies[ three copies of a particular chromosomes] are compatible with survival to term with chromosomes 13, 18, and 21.

8. Non Disjunction

9. Non Disjunction

10. Autosomal Chromosome Problems

11. Down Syndrome (Trisomy 21) • The result of an extra copy of chromosome 21. People with Down syndrome are 47, 21+. • Down syndrome affects 1:700 children and alters the child's phenotype either moderately or severely: • characteristic facial features, short stature; heart defects • susceptibility to respiratory disease, shorter lifespan • often sexually underdeveloped and sterile, usually some degree of mental retardation. • Down Syndrome is correlated with age of mother but can also be the result of nondisjunction of the father's chromosome 21.

13. Down Syndrome (Trisomy 21)

14. Patau syndrome(Trisomy 13) Serious eye, brain, circulatory defects as well as cleft palate. 1:5000 live births. Children rarely live more than a few months.

15. Patau syndrome(Trisomy 13)

16. Edwards Syndrome (Trisomy 18) • Almost every organ system affected 1:10,000 live births. Children with full Trisomy 18 generally do not live more than a few months.

17. DiGeorge syndrome(Monosomy 22)22q11.2 deletion syndrome • Congenital thymic aplasia, and thymic hypoplasia • Is a syndrome caused by the deletion of a small piece of chromosome 22. • The deletion occurs near the middle of the chromosome at a location designated q11.2 • Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems

18. DiGeorge syndrome

19. Precursor T cell differentiation defect • Lack of T helper (Th) cells , Cytotoxic T cells (CTL) and T regulatory (Treg) cells • B cells are present but T-dependent B cell responses are defective • Anti-viral and anti-fungal immunity impaired • Developmental defect in the 3rd and 4th pharyngeal pouch • Results in facial defect and congenital heart disease • Treated with thymic transplant • Autosomal dominant trait

20. Which of the following is an example of monosomy? • 46,XX • 47,XXX • 69,XYY • 45,X

21. Sex Chromosome(X Y) Abnormalities Male Sex Female Sex

22. X Chromosome

23. Y Chromosome

24. Sex Chromosome Abnormalities • The majority of known types of chromosomal abnormalities involve Sex chromosomes. • In frequency of occurrence, they are only slightly less common than autosomal abnormalities.  • However, they are usually much less severe in their effects.  • Sex chromosome abnormalities are gender specific. 

25. Male Sex 1. Klinefelter Syndrome

26. Male Sex 1. Klinefelter Syndrome • Klinefelter syndrome: males inherit one or more extra X chromosomes--their genotype is XXY.  • They characteristically have relatively high-pitched voices, asexual to feminine body contours as well as breast enlargement, and comparatively little facial and body hair.  • They are sterile or nearly so, and their Testes and Prostat glamds are small.  As a result, they produce relatively small amounts of testosterone.

27. 2. XYY Syndrome • XYY syndrome males inherit an extra Y chromosome, their genotype is XYY.  • As adults, these "super-males" are usually tall (above 6 feet) and generally appear and act normal.  • However, they produce high levels of testosterone.  • During adolescence, they often are slender, have severe facial acne, and are poorly coordinated.  • They are usually fertile and lead ordinary lives as adults. 

28. 2. XYY Syndrome

29. Female Sex 1. Turner syndrome

30. Female Sex 1. Turner syndrome • Turner syndrome occurs when females inherit only one X chromosome--their genotype is X0. •   If they survive to birth, these girls have abnormal growth patterns.  • They are short in stature, averaging 4 foot 7 inches as adults, and often have distinctive webbed necks (i.e., extra folds of skin), small jaws, and high arched palates.  • They generally lack prominent female secondary sexual characteristics.  They have exceptionally small, widely spaced breasts, broad shield-shaped chests, and turned-out elbows.  • Their ovaries do not develop normally and they do not ovulate. 

31. Female Sex 1. Turner syndrome

32. 2. Triple-X females • Inherit three X chromosomes--their genotype is XXX or more rarely XXXX or XXXXX.  As adults, these "super-females" are usually an inch or so taller than average with unusually long legs, but otherwise appear normal.  • They have normal development of sexual characteristics and are fertile.  They may have slight learning difficulties and are usually in the low range of normal intelligence (especially the XXXX and XXXXX individuals). 

34. Mosaicism and Chimerism • Mosaics and chimeras are persons that have more than one genetically-distinct population of cells. • In mosaics, the genetically different cell types all arise from a single zygote. • In chimeras originate from more than one zygote.

35. Chromosome instability syndromes • They are a group of inherited conditions associated with chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies. • The following chromosome instability syndromes are known: • Ataxia Telagiectasia • Bloom Syndrome • FanconiAnaemia

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