Question

You are a Genetic Counsellor/Researcher working in the Medical Genetics Unit of a hospital. A proband has been referred to you from one of the clinical consultants in the metabolic unit. It appears to be a novel Mendelian disease and it is your job to further investigate the genetic basis of the condition.

How would you determine if this mutation arose once or multiple times if given access to the DNA from different pedigrees with this disease?

Answer 1

It is quite easy to identify the frequency and pattern of mutations if you have access to the DNA from various pedigrees with this disease. Comparing the DNA sequence of the diseased with normal genome can recognize the mutations since the human genome is already sequenced by the Human Genome Project. Models of mendelian disorders are autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y linked.
Gene mapping can be used to identify the frequency of mutation in pedigrees. If you are suspecting somebody with a mendelian disorder, you can trace back his family tree and analyze their pedigree for the suspecting mutation. Complete pedigree analysis of the particular allelic expression by gene mapping will help you to recognize the pattern of inheritance of mutation. Do the same analysis for other pedigrees (family trees) with the same kind of phenotypes, to confirm the nature of inheritance whether it is X or Y linked, autosomal recessive or dominant, etc..