Disease gene identification

Disease gene identification is a process by which scientists identify the mutant genotypes responsible for an inherited genetic disorder.

Knowledge of which genes (when non-functional) cause which disorders will simplify diagnosis of patients and provide insights into the functional characteristics of the mutation.

The advent of modern-day high-throughput sequencing technologies combined with insights provided from the growing field of genomics is resulting in more rapid disease gene identification, thus allowing scientists to identify more complex mutations.

The differences between most disease gene identification procedures are in the second step (where DNA samples are analyzed and screened to determine regions in which the mutation could reside).

Such a small population, possibly created by the founder effect, will have a limited gene pool, and thus any inherited disease will probably be a result of two copies of the same mutation segregating on the same haplotype.

Homozygous blocks in the genomes of affected individuals can then be laid on top of each other, and the overlapping region should contain the disease gene.

By taking into consideration the population allele frequencies for all SNPs via autozygosity mapping, the results of homozygosity can be confirmed.

[8] After the systematic knockout is completed (and possibly confirmed by mRNA expression analysis), the phenotypic results of the knockdown/knockout can be observed.

After filtering out all known benign polymorphisms, synonymous changes, and intronic changes (that do not affect splice sites), only potentially pathogenic variants will be left.