In this article we will discuss about the examples of genetic linkage in humans. Also learn its clinical applications.
1. Nail-Patella Syndrome and ABO Blood Groups:
This genetic linkage has been demonstrated by Reneisck and Lawler (1955). The nail- patella syndrome or hereditary onychosteodysplasia is characterised by a constellation of abnormalities. The nail dystrophy is variable, ranging from a triangular lunule, through moderate abnormality with discoloration, a longitudinal crack and reduced size, and, finally, to severe dystrophy with absence of a large part of the nail. Thumb and index finger and first and second toes are especially affected.
The patellae are usually rudimentary or may be absent altogether. Some of the affected persons exhibit curious conical bony projections from the middle of the iliac bone, known as iliac horns. The elbows also often show abnormalities.
Like this, the abnormalities are numerous but they are not very severe and length of the life and fertility do not appear to be affected. This nail-patella syndrome is due to a dominant gene showing perfect regularity of transmission. The perfect regularity of transmission means affected persons always have an affected parent and the mating affected X normal gives affected and normal offspring in equal proportion.
An analysis of the pedigree of nine family groups indicated that the locus for the nail-patella gene is situated on the same chromosome as the ABO locus and their distance apart is about 10 unit of crossing over. It should be remembered here that the nail-patella gene is not associated with any particular ABO gene.
In some family it is found to be on a chromosome containing B gene, in some other on a chromosome containing the O gene and in some exceptional cases it has been to the A gene. Taking the children of affected parents in different pedigrees, the distribution of blood groups amongst nail-patella syndrome and normal are as follows:
2. Linkage of the HLA Loci:
The region on the chromosome 6 that carries the major histocompatibility complex is now known as HLA. The different gene loci are designated as A, B, C, D and the specificities or alleles at each locus are identified by numbers 1, 2, 3 etc. The actual order of the loci is thought to be D, B, C, A and are situated close to each other and, therefore, the alleles at each of these four loci will nearly always be inherited together.
The particular combination of specificities on the same chromosome is called the haplotype and the haplotype of one chromosome is not of course necessarily the same as the other chromosome. In one study of 1,362 children whose parents had been typed, it was found that only 11 children had recombinant haplotypes. The crossing over occurs only between locus A and B.
The following is the schematic representation of the gene map of part of the short arm of the chromosome 6 showing the arrangement of HLA loci:
3. Linkage between Lutheran and Secretor Types:
This linkage group has already been detected but the chromosome pairs remain unidentified. These are at least two alleles at the Lutheran locus (Lu) which denote antigenic differences in the blood.
The dominant secretor allele allows the detection of the blood group antigen A and /or B in the saliva. It has been demonstrated by studying several pedigree that there is a fairly close linkage between Lu and Se loci. However, according to Green- wait (1955) Lu and Se are 16 unit apart i.e. 16% recombination occurs between Lu and Se.
4. Linkage between Duffy Blood Type and Lamellar Cataract:
There is a special type of blood antigen known as Duffy antigen due to the presence of a gene Fy in the population of Great Britain and Negroes. This antigen is harmless. Lamellar cataract is a particular form of eye defect due to presence of a dominant gene. According to Renwick and Lawler there is a linkage between Duffy antigen gene and cataract gene.
Clinical Applications of Genetic Linkage:
(i) Helps to find marker genes that are linked to serious dominant conditions.
(ii) Helps in the prenatal diagnosis of severe dominant condition where the presence or absence of marker gene could be detected in amniotic fluid.
(iii) Genetic marker would generally be a series of alleles at a locus that is closely linked to the particular disease gene, and the closer it is the better it is as a marker, because uncertainty due to possible crossing over between the marker and disease genes is reduced to a minimum.
(iv) Genetic linkage does not imply that the disease in general is associated with any particular allele.
(v) Genetic linkage helps in predictions on the transmission of the disease in small family pedigrees.
(vi) Of course, the prediction cannot be made with 100% accuracy of the possibility of a crossing over.
