Human Chromosomes and Chromosome Behavior 1 Karyotype stained
Human Chromosomes and Chromosome Behavior 1
Karyotype = stained and photographed preparation of metaphase chromosomes arranged according to their size and position of centromeres 2
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. 3
Centromeres • Chromosomes are classified according to the relative position of their centromeres • Chromosomes with no centromere, or with two centromeres, are genetically unstable 4
Chromosomal Abnormalities
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 6
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 7
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 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 8
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 9
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 10
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 11
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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) 13
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 14
Trisomy 18 • • Incidence 1/8000 Overlaps with trisomy 13 Sever Mental retardation >90% dead in 1 st year 15
Trisomy 18 • • Small face with prominant occiput Small sternum and pelvis Flexion deformity of the finger VSD and horseshoe kidney 16
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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 23
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Trisomy 13 • Sever developmetal retardation • Incidence 1/20000 • 90% dead in the 1 st year 25
Trisomy 13 • • Midline brain defect Malformed ear Microophalmos and coloboma Scalp defect 26
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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 31
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 32
INVERSIONS A B C C B A B B A A C C 33
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 34
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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 36
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 37
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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 39
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 40
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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 b 15 q 11 q 13, maternal in origin • Paternal uniparental disomy 42
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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 44
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