Chromosomal Abnormalities

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

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

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

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

• Karyotype – photographs of chromosomes from rapidly dividing cells are paired up and analyzed for chromosomal defects

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

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

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

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

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