Bio101 Chromosomal Alterations

NONDISJUNCTION

Normally, meiosis separates things cleanly. Sometimes it does not

In nondisjunction

homologous pairs fail to separate in meiosis I, or sister chromatids fail to separate in meiosis II. One gamete ends up with two copies of a chromosome; another ends up with none

Look at the figure.

Panel (a) is meiosis I failure — all four gametes are abnormal. Panel (b) is meiosis II failure — two of four are.

NONDISJUNCTION- the chromosomes are normal

the division went wrong

ANEUPLOIDY

if an abnormal gamete is fertilized, the zygote has the wrong number of a chromosome. That is aneuploidy.

ANEUPLOIDY- Trisomic

three copies of a chromosome, 2n + 1

ANEUPLOIDY- Monosomic

one copy, 2n - 1

ANEUPLOIDY- Polyploidy is a different thing

more than two complete sets. Lethal in mammals; common and often useful in plants.

ANEUPLOIDY- Most human aneuploidies end in early pregnancy loss

Only a few are survivable

DOWN SYNDROME

TRISOMY 21

DOWN SYNDROME (TRISOMY 21)

Three copies of chromosome 21 — the smallest human autosome

DOWN SYNDROME (TRISOMY 21)- It affects about

one in 830 children born in the United States

DOWN SYNDROME (TRISOMY 21)- Count the chromosomes in the karyotype

47, with three at position 21

DOWN SYNDROME (TRISOMY 21)- Why is this one survivable when most trisomies are

not?

Chromosome 21 is small and carries relatively few genes, so the dosage imbalance is smaller.

MATERNAL AGE AND NONDISJUNCTION

The frequency of trisomy 21 rises sharply with the age of the egg-producing parent. Under 30 it is well under 1 in 1,000. By 40 it is roughly 1 in 100

MATERNAL AGE AND NONDISJUNCTION- And here is the mechanism — call back to Chapter 10

Human oocytes are arrested in prophase I from before birth until ovulation.

MATERNAL AGE AND NONDISJUNCTION- An egg ovulated at 40 has been paused mid-meiosis for forty years

The proteins holding the chromosomes together degrade over time.

Understanding MATERNAL AGE AND NONDISJUNCTION

That is why the risk is age-dependent on one side and not the other

Aneuploidy of the sex chromosomes(SEX CHROMOSOME ANEUPLOIDY)

upsets the genetic balance much less than autosomal aneuploidy

SEX CHROMOSOME ANEUPLOIDY- Part of the reason is X inactivation

extra X chromosomes get largely silenced, and the Y carries few genes

Klinefelter syndrome

(XXY, about 1 in 500 male births): male, often taller, usually sterile

Turner syndrome

(X0, monosomy X): female, short stature, sterile without treatment — the only viable human

monosomy

SEX CHROMOSOME ANEUPLOIDY

XYY males and trisomy X females often have no defined syndrome at all

A chromosome can physically break, and the pieces can rejoin wrongly. Four outcomes:

Deletion, Duplication, Inversion, Translocation

Deletion

a segment is lost

Duplication

a segment is repeated

Inversion

a segment is reversed end to end

Translocation

a segment moves to a nonhomologous chromosome

FOUR WAYS STRUCTURE BREAKS

Deletions and duplications change gene dosage.Inversions and translocations usually do not — they move genes to a new neighborhood

DELETION: CRI DU CHAT

a deletion removes every gene in the lost segment. An embryo homozygous for a large deletion is usually not viable.

Cri du chat

"cry of the cat" — results from a specific deletion on chromosome 5

Cri du chat — "cry of the cat"

Affected children have a distinctive high-pitched cry in infancy, severe intellectual disability, and a small head

Cry of the cat?

No gene is mutated here. The genes are simply gone, and the dosage is halved

TRANSLOCATION: PHILADELPHIA

A reciprocal translocation swaps segments between two nonhomologous chromosomes

The Philadelphia chromosome

a piece of chromosome 9 and a piece of chromosome 22 trade places

TRANSLOCATION: PHILADELPHIA- The break points fall

____inside two genes, and the fusion creates a new hybrid gene that signals the cell to divide

constantly

TRANSLOCATION: PHILADELPHIA- result

The result is chronic myelogenous leukemia — and because we know the exact fusion, there is a drug that targets it specifically

Nondisjunction

in meiosis I or II produces gametes with the wrong chromosome number

Aneuploidy

trisomy is 2n + 1, monosomy is 2n − 1. Trisomy 21 is the common survivable autosomal case, and the risk rises with the age of the egg

Four structural changes

deletion, duplication, inversion, translocation

Cri du chat is ___; the Philadelphia chromosome is a translocation that

a deletion, causes leukemia