Chromosomes: normal and aberrant structure and karyotypes

Chromosomes are comprised of a single, uninterrupted DNA molecule complexed with proteins (histones and others).

Landmarks of human chromosome structure include telomeres and the centromere demarcating the two “arms” (p and q).

A karyotype is a visual display of the chromosomes of an individual.– A human karyotype is generally prepared from cultured white

blood cells treated with a mitogen and then colchicine to arrest cells in mitotic metaphase (chromosomes highly condensed and visible). Cells are then swollen hypotonically and chromosomes released onto a slide and then stained to reveal species-specific banding patterns of individual chromosomes. FISH can be performed for mapping.

Klug and Cummings, 6th Ed., 2000

Chromosome numerical variations Polyploidy: extra complete sets of

chromosomes, e.g., 3n (triploidy). This is found in some spontaneously aborted human fetuses.

Aneuploidy:”wrong number” of chromosomes, e.g., – 2n + 1 = trisomy, the presence of an extra copy of

one specific chromosome– 2n - 1 = monosomy, the absence of one copy of a

specific chromosome– Origins of aneuploidy most frequently lie in meiotic

nondisjunction

Common human aneuploidies

There are no viable human monosomies except that of the X chromosome: XO, Turner syndrome.

Other sex-chromosome aneuploidies associated with viability are XXY (Klinefelter syndrome) and XYY.

Most human autosomal trisomies are embryonic lethals, but Ts 13, 18 and 21 survive in many cases.

The most viable human trisomy is Ts21, Down syndrome. Incidence of nondisjunction-related Ts21 increases with increasing maternal age.

Abnormalities and lethality associated with monosomy and trisomy suggest tight dosage control, with no dosage compensation.

Chromosomal structural aberrations The most frequent structural aberrations

include: deletions, duplications, inversions, and translocations.

These abnormalities of structure can give rise to abnormalities in meiotic segregation of chromosomes as well as further structural abnormalities after crossing over.

Translocations can be reciprocal or non-reciprocal, or Robertsonian centric fusions.

Chromosome structure and

aberrations: Summary Important landmarks of chromosome structure

includes telomeres, a centromere and the arms. Construction of karyotypes enables not only

cytogenetic analysis of defects but also gene mapping (e.g., by FISH).

Aberrations of chromosome number include polyploidy and aneuploidy, but aneuploidy is much more common in humans.

Aberrations of structure include inversions, deletions, duplications and translocations, both reciprocal and non-reciprocal. These can be useful reagents for gene mapping.