Research updates
15 - Ethics and the Gene Map page 2
Go back a page
Go forward a page
2. How is gene mapping done? Link to the Medical Research Council web site
The 23 pairs of chromosomes
 
Remarkably, it was only in 1956 that it became known that humans have 23 pairs of chromosomes. We have come a long way since then! Even before 1956, however, the identities of many human genes carried on the X chromosome were known. The reasons for this is that conditions, such as red-green colour-blindness and haemophilia, that result from recessive X-linked mutations are much more common in males than in females. This results from the fact the males, possessing the sex chromosomes X and Y, carry only one copy of the X chromosome in each cell and so are effectively haploid for it.
 
Figure 22 Standard human karyotype. The chromosomes are stained, which produces characteristic bands, and then photographed and rearranged in order of length. Chromosome-1 is the longest and chromosome-21 the shortest. Is this karyotype from a male or a female?

 

22212019181716151413121110987654321
 
Females, however, have two copies of the X chromosome and so are diploid for this chromosome as they (and males) are for the 22 autosomal pairs.

A female who is heterozygous for a recessive mutation on the X chromosome does not manifest the condition associated with the mutation. The normal dominant allele masks the effect of the recessive allele. A male, however, who has the recessive mutant allele has no normal dominant allele to mask its effect. His phenotype therefore shows the mutation.

   
Go back a page Go to the top of the page Go forward a page
Question 2

Approximately 8% of the alleles at the locus that controls red-green colour vision are mutant in humans. The locus on the X chromosome and the mutant alleles are recessive.

a) What percentage of the alleles at this locus will be normal?
b) What percentage of men would you expect to be red-green colour-blind?
c) What percentage of women would you expect to be red-green colour blind?
d) What difference would it make if a mutant X-linked allele was dominant?  

 

So it is relatively easy to find out which genes are on the X chromosome. But what about the autosomal chromosomes? The first time a gene was mapped to an autosomal chromosome was in 1968. Roger Donahue, then a research student, looked at his own chromosomes under a microscope and found that one of his chromosomes-1 was slightly longer than in most people. Further research revealed that all the members of his family who had this longer version of chromosome-1, also carried the allele for a particular type of blood group called Duffy-a. All the members of his family who had the normal chromosome-1 did not have this allele. This provides strong evidence that the locus for this gene is linked to this tiny extra bit of chromosome-1. This approach soon led to many other genes being assigned to human autosomal chromosomes.

However, this approach relies on finding visible chromosome mutations - typically deletions, duplications or translocations. A much more efficient way of gene mapping human genes to chromosomes arrived with the advent of human-mouse hybrid cells called somatic cell hybrids. It is possible to fuse a somatic (i.e. diploid, no-germline) human cell with a somatic mouse cell and establish a resulting cell line which reproduces itself by mitosis. Perhaps unsurprisingly though, such a cell line has problems maintaining its full chromosome complement. Over time, it tends to lose chromosomes. You can therefore end up with cell lines which have a lot of mouse chromosomes but only one pair of human chromosomes, e.g. chromosome-4.

This means that any human proteins that this cell line makes must be coded for by genes on human chromosome-4. Somatic cell hybridisation and other more recent approaches have meant that human gene mapping, while still involving a great deal of hard work, is becoming increasingly routine.