1. 1 Human Chromosomes and Chromosome Behavior

2. 2 Karyotype = stained and photographed preparation of metaphase chromosomes arranged according to their size and position of centromeres

3. 3 Human Chromosomes Each chromosome in karyotype is divided into two regions (arms) separated by the centromere p = short arm (petit); q = long arm p and q arms are divided into numbered bands and interband regions based on pattern of staining Within each arm the regions are numbered.

4. 4 Centromeres Chromosomes are classified according to the relative position of their centromeres Chromosomes with no centromere, or with two centromeres, are genetically unstable

5. Chromosomal Abnormalities

6. 6 Mistakes during segregation During anaphase, homologous chromosomes separate Sometimes, they do not separate, leading to the formation of a gamete with two copies of one chromosome Called Nondisjunction After fertilization, the zygote will have 3 copies of one chromosome – called trisomy

7. 7 Can occur during meiosis: During the S phase of cell cycle – mistakes in making sister chromatids. During prophase 1 – when crossing over occurs During anaphase 1 – separation of homologous pairs During anaphase 2 – separation of sister chromatids

8. 8 Four types of errors in gene sequence Deletion: Gene sequence 1 2 3 4 5 goes to 1 2 4 5; 3 deleted Duplication: Gene sequence 1 2 3 4 5 goes to 1 2 3 2 3 4 5; section 2,3 copied twice –(during crossover, can get one chromosome with deletion & one with duplication) Inversion: 1 2 3 4 5 goes to 1 2 5 4 3 –One segment is turned around so order reversed Translocation: 1 2 3 4 5 goes to 1 2 3 8 9 4 5 –A segment from another place or another chromosome is inserted in a gene sequence

9. 9 Two types of prenatal testing Amniocentesis – remove amniotic fluid from around fetus; culture cells; do karyotype Chorionic villi sampling – extensions of placenta growing into uterus, sample tissue and do karyotype

10. 10 Chromosomal Disorders Trisomy – an extra copy of one chromosome; results from non-disjunction –Trisomy 21 – Down Syndrome (mental retardation) –Trisomy 18 – Edwards Syndrome (1/10,000); thin, frail, feeding problems –Trisomy 13 – Patau Syndrome (1/5000) Translocation Down (etc) – extra chromosome linked to another (usually 21, 13, 22, 15) – can be inherited Mosaic – disorder appears in some body cells, but not all

11. 11 Down Syndrome Incidence 1/700 2/3 of down fetus spontaneously abort Trisomy 21 in 94% of cases with extra chromosome from mother mostly(95%) Risk correlate with maternal age –<25 y/o 1/1600 –>40 y/0 1/80 2% are mosaic

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13. 13 Other Clinical features Hypotonia without weakness –Hypotonia is a disorder that causes low muscle tone (hypotonic condition) Clinodactaly protruded tongue,small ears,brachycephaly,small up turned nose, depressed nasal bridge. Mental retardation, socially do better with good environment (Happy children)

14. 14 Clinical issues Cardiac and GI Hypothyriodism Transient leukemoid reaction Alzheimer’s disease up to 25% over 40 y/o Early death relate to cardiac dysfunction

15. 15 Trisomy 18 Incidence 1/8000 Overlaps with trisomy 13 Sever Mental retardation >90% dead in 1 st year

16. 16 Trisomy 18 Small face with prominant occiput Small sternum and pelvis Flexion deformity of the finger VSD and horseshoe kidney

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23. 23 triploidy Complete extra set of chromosomes Mostly miscarriages Fetal wastage skeleton more than cephalic, 2% survive to be recognized Large hydatidiform placenta Genital and CNS abnormalities

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25. 25 Trisomy 13 Sever developmetal retardation Incidence 1/20000 90% dead in the 1 st year

26. 26 Trisomy 13 Midline brain defect Malformed ear Microophalmos and coloboma Scalp defect

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31. 31 Deletions Cri-du-chat – deletion in chromosome 5; mental retardation; delayed development; low birthweight; small head; poor muscle tone; high pitched cry D-George syndrome – deletion on chromosome 22; congenital heart disease; cleft palate; learning difficulties Prader-Willi (from Mom)/Angelman (from Dad) – deletion in chromosome 15; different symptoms – PW mental retardation; short; obese; small hands & feet; - Angelman jerky movements; inappropriate laughter

32. 32 Duplications Pallister Killian – duplication in chromosome 12; mental retardation, coarse facial features, prominent forehead, thin upper lip, thick lower lip, hearing impaired; may live until 40

33. 33 A B C C B A B B A A C C INVERSIONS

34. 34 Female Abnormalities Turner Syndrome – only one X chromosome (XO); short, webbed necks, small jaws; lack prominent female sex characteristics; do not ovulate (1/3000 to 1/5000 live female births) Metafemales – 1 or more extra X chromosomes; taller than average w/ long legs, slender torsos 1/1000 live births

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36. 36 Male Abnormalities Klinefelter syndrome – males w/ one or more extra X chromosomes – high pitched voices, breast enlargement, sterile, testes & prostate are small; treat w extra testosterone XYY syndrome – super-males; tall, seem normal; can live normal lives

37. 37 Klinefelter syndrome 20% of aspermic adult male (blocked spermatogenesis 47 XXY in 80% and mosaic in 20% IQ is 98 (normal) with mild decrease in verbal IQ Scoliosis, decrease libido may improve with testesterone, gynecomastia

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39. 39 Fragile X Syndrome Moderate to sever mental retardation Speech delay, short attention, hyperactivity Poor motor coordination and mouthing objects Poor socialization, temper tantrum Mood disorder (bipolar), schizophrenia

40. 40 Fragile X syndrome Long protruding ears Long face and prominent jaw Flattened nasal bridge High arch palate Macroorchidism Genetic is complex, 80% penetration in male and 30% penetration in female

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42. 42 Angelman syndrome Severe mental retardation Inappropriate laughter Decrease pigmentation of choroid or iris (pale blue eyes) Ataxia and jerky eye movement Sever speech proplem Deletion of b15q11q13, maternal in origin Paternal uniparental disomy

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44. 44 Prader-willi syndrome (A fat red faced boy in state of somnolency) Charles Diickens Early hypotonia Obesity Short stature as adult Almond shaped blue eyes Mental retardation (mild to moderate) Narrow hands

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