Chromosome Disorders: Introduction

In humans, the normal diploid number of chromosomes is 46, consisting of 22 pairs of autosomal chromosomes (numbered 1–22 in decreasing size) and one pair of sex chromosomes (XX in females and XY in males). The genome is estimated to contain between 30,000 and 40,000 genes. Even the smallest autosome contains between 200 and 300 genes. Not surprisingly, duplications or deletions of chromosomes, or even small chromosome segments, have profound consequences on normal gene expression, leading to severe developmental and physiologic abnormalities.

Deviations in number or structure of the 46 human chromosomes are astonishingly common, despite severe deleterious consequences. Chromosomal disorders occur in an estimated 10–25% of all pregnancies. They are the leading cause of fetal loss and, among pregnancies surviving to term, the leading known cause of birth defects and mental retardation.

In recent years, the practice of cytogenetics has shifted from conventional cytogenetic methodology to a union of cytogenetic and molecular techniques. Formerly the province of research laboratories, fluorescence in situ hybridization (FISH) and related molecular cytogenetic technologies have been incorporated into everyday practice in clinical laboratories. As a result, there is an increased appreciation of the importance of "subtle" constitutional cytogenetic abnormalities, such as microdeletions and imprinting disorders, as well as previously recognized translocations and disorders of chromosome number.

Reff:

Harrison's Internal Medicine > Chapter 63. Chromosome Disorders >