Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4% of African Americans causes lethal recessive osteogenesis imperfecta
Genetics in Medicine, Volume 14, No. 5, Year 2012
Notification
URL copied to clipboard!
Description
Purpose: Deficiency of prolyl 3-hydroxylase 1, encoded by LEPRE1, causes recessive osteogenesis imperfecta (OI). We previously identified a LEPRE1 mutation exclusively in African Americans and contemporary West Africans. We hypothesized that this allele originated in West Africa and was introduced to the Americas with the Atlantic slave trade. We aimed to determine the frequency of carriers for this mutation among African Americans and West Africans, and the mutation origin and age. Methods: Genomic DNA was screened for the mutation using PCR and restriction digestion, and a custom TaqMan genomic single-nucleotide polymorphism assay. The mutation age was estimated using microsatellites and short tandem repeats spanning 4.2 Mb surrounding LEPRE1 in probands and carriers. Results: Approximately 0.4% (95% confidence interval: 0.22-0.68%) of Mid-Atlantic African Americans carry this mutation, estimating recessive OI in 1/260,000 births in this population. In Nigeria and Ghana, 1.48% (95% confidence interval: 0.95-2.30%) of unrelated individuals are heterozygous carriers, predicting that 1/18,260 births will be affected with recessive OI, equal to the incidence of de novo dominant OI. The mutation was not detected in Africans from surrounding countries. All carriers shared a haplotype of 63-770 Kb, consistent with a single founder for this mutation. Using linkage disequilibrium analysis, the mutation was estimated to have originated between 650 and 900 years before present (1100-1350 CE). Conclusion: We identified a West African founder mutation for recessive OI in LEPRE1. Nearly 1.5% of Ghanians and Nigerians are carriers. The estimated age of this allele is consistent with introduction to North America via the Atlantic slave trade (1501-1867 CE). ©American College of Medical Genetics and Genomics.
Authors & Co-Authors
Cabral, Wayne A.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Barnes, Aileen M.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Adeyemo, Adebowale A.
United States, Bethesda
National Human Genome Research Institute Nhgri
Cushing, Kelly
United States, Bethesda
National Human Genome Research Institute Nhgri
Chitayat, David A.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
Hospital for Sick Children University of Toronto
Canada, Toronto
University of Toronto
Porter, Forbes D.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Panny, Susan R.
United States, Baltimore
Dhmh
Gulamali-Majid, Fizza
United States, Baltimore
Dhmh
Tishkoff, Sarah A.
United States, Philadelphia
University of Pennsylvania
Rebbeck, Timothy R.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Guèye, Sérigne Maguèye
Senegal, Dakar
Hopital Général de Grand Yoff
Bailey-Wilson, Joan E.
United States, Bethesda
National Human Genome Research Institute Nhgri
Brody, Lawrence C.
United States, Bethesda
National Human Genome Research Institute Nhgri
Rotimi, Charles N.
United States, Bethesda
National Human Genome Research Institute Nhgri
Marini, Joan C.Bodurtha
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Statistics
Citations: 48
Authors: 15
Affiliations: 9
Identifiers
Doi:
10.1038/gim.2011.44
e-ISSN:
15300366
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Study Locations
Multi-countries
Ghana
Nigeria