In a study, a team of investigators based mainly at Stanford University School of Medicine, have introduced ethnicity-specific reference genome sequences. Their usefulness was demonstrated in examining the genomes of a family of four and following the flow of genes, especially genes connected with disease risk, from one generation to the next. The investigation is to be published in the open-access journal PloS Genetics on September 15th.
They argued that the widely-used human reference genome (the result of the Human Genome Project), is deficient in the most common variants at 1.6 million genomic positions, out of which 4000 affect disease risk. For the present investigation the researchers used published genetic information from hundreds of unrelated individuals, in order to develop three ethnicity-specific reference genomes, each including the most frequent variants for that group. The investigators discovered that by comparing people’s genome to one that is ethnically matched and contains the most common variations, it helps in the detection of rare disease risk variants and lowers the number of errors in finding out each individual’s exact genome sequence.
The group were able to estimate the mean mutation rate in the human population by using the genomes of the four person family, and more finely locate the mixing of chromosomes, a process that maximizes genetic diversity across generations. The characterization of flow of genetic data enabled the identification of sequencing errors and, in specific, genetic risk factors linked with predisposition to blood clot formation and response to blood-thinning medications. In addition, a sequence-based methodology for Human Leukocyte Antigen (HLA) typing was presented. HLA types are the sets of variable immune system genes that determine pathogen recognition, and they are connected with many disease traits including autoimmune diseases and psoriasis, of which all four family members are at high risk.
They advise that, as the cost for whole-genome sequencing reduces, the need to understand these data increased. They conclude:
“The ethnicity-specific, family-based approaches to interpretation of individual genetic profiles are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.”
Written by Grace Rattue