The population genetics of chronic kidney disease: insights from the MYH9-APOL1 locus.
Summary of "The population genetics of chronic kidney disease: insights from the MYH9-APOL1 locus."
Many rare kidney disorders exhibit a monogenic, Mendelian pattern of inheritance. Population-based genetic studies have identified many genetic variants associated with an increased risk of developing common kidney diseases. Strongly associated variants have potential clinical uses as predictive markers and may advance our understanding of disease pathogenesis. These principles are elegantly illustrated by a region within chromosome 22q12 that has a strong association with common forms of kidney disease. Researchers had identified DNA sequence variants in this locus that were highly associated with an increased prevalence of common chronic kidney diseases in people of African ancestry. Initial research concentrated on MYH9 as the most likely candidate gene; however, population-based whole-genome analysis enabled two independent research teams to discover more strongly associated mutations in the neighboring APOL1 gene. The powerful evolutionary selection pressure of an infectious pathogen in West Africa favored the spread of APOL1 variants that protect against a lethal form of African sleeping sickness but are highly associated with an increased risk of kidney disease. We describe the data sources, process of discovery, and reasons for initial misidentification of the candidate gene, as well as the lessons that can be learned for future population genetics research.
Affiliation
Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv 69978, Israel.
Journal Details
This article was published in the following journal.
Name: Nature reviews. Nephrology
ISSN: 1759-507X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21537348
- DOI: http://dx.doi.org/10.1038/nrneph.2011.52
Medical and Biotech [MESH] Definitions
Renal Insufficiency, Chronic
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Hydronephrosis
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.
Kidney Failure
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal failure, either acute (KIDNEY FAILURE, ACUTE) or chronic (KIDNEY FAILURE, CHRONIC), requires HEMODIALYSIS.
Pyelonephritis, Xanthogranulomatous
A chronic inflammatory condition of the KIDNEY resulting in diffuse renal destruction, a grossly enlarged and nonfunctioning kidney associated with NEPHROLITHIASIS and KIDNEY STONES.
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