Other genetic disorders

Other genetic disorders

The human genome consists of 23 pairs of chromo-somes carrying an estimated 30 000 genes. The pairs of matching chromosomes as seen at colchicine-arrested metaphase are numbered in accordance with their size. A centromere divides each chromosome into a shorter (p) and a longer (q) arm.

Any individual’s chromosomal make-up (karyotype) can be expressed as their total number of chromosomes plus their sex chromosome constitution. A normal male therefore is 46XY. A shorthand notation exists for recording other abnormalities such as chromosome translocations and deletions.

The precise location of any gene can be given by naming the chromosome, the arm of the chromosome (p or q), and the numbers of the band and subband of the chromosome, as seen with Giemsa staining, on which it lies. One of the genes important for atopy, for instance, lies on chromosome 11q13, i.e. on the long arm of chromosome 11 at band 13.

Several techniques can be used to identify the posi-tion of a gene.

1. A clue maybe offered by finding that some affected individuals have chromosomal deletions or unbalanced translocations, suggesting that the gene in question lies on the abnormal segments.

2. Linkage analysis. Genes are linked if they lie closetogether on the same chromosome; they will then be inherited together. The closer together they are, the less is the chance of their being separated by cross-overs, one to six of which, depending on length, occur on each chromosome at meiosis. Each member of an affected family has to be examined both for the pres-ence of the trait to be mapped, and also for a marker, usually a DNA probe, which has already been mapped. If linkage is established then the two loci will be close on the same chromosome. The probability of the results of such a study representing true linkage can be expressed as a logarithm of the odds (Lod) score. A score of three or more suggests that the linkage is likely to be genuine.

3. Somatic cell hybridization. A hybrid made by fus-ing a human cell with a mouse cell will at first have two sets of chromosomes. Later human chromosomes are lost randomly until a stable state is reached. Those cells that produce a particular human protein must contain the relevant chromosome. A panel of such hybrid cells can be created which differ in their con-tent of human chromosomes. By comparing these, the chromosomal site of the relevant gene can be deduced.

4. In situhybridization. A cloned sequence of DNA, ifmade single-stranded by heat, will anneal to its com-plementary sequence on a chromosome. Radioactive or fluorescent labelling can be used to indicate its position there.