Understanding rare disease pathogenesis: a grand challenge for model organisms

Abstract

In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS.

Figure 1

Number of novel genes discovered by whole-exome sequencing (WES) or whole-genome sequencing (WGS). This graph represents the results of PubMed searches using the terms “exome sequencing” and “whole genome sequencing,” sorted by date of publication and filtered for only single-gene diseases (references to complex diseases and cancer were excluded). Results were sorted to identify those that reported novel gene discovery, and duplicates were removed. The number of novel disease genes identified using WES is significantly greater than that by WGS. Reprinted with permission from: Boycott K. M., D. A. Dyment, S. L. Sawyer, M. R. Vanstone, and C. L. Beaulieu, 2014 Identification of genes for childhood heritable diseases. Annu. Rev. Med. 65: 19–31. PMID: 24422568.