Frequency of rare allelic variation in candidate genes among individuals with low and high urinary calcium excretion

Our study investigated the association of rare allelic variants with extremes of 24-hour urinary calcium excretion because higher urinary calcium excretion is a dominant risk factor for calcium-based kidney stone formation. We resequenced 40 candidate genes potentially related to urinary calcium exc...

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Bibliographic Details
Published in:PloS one 2013-08, Vol.8 (8), p.e71885
Main Authors: Toka, Hakan R, Genovese, Giulio, Mount, David B, Pollak, Martin R, Curhan, Gary C
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Biology
Calcium
Calcium (urinary)
Calcium - urine
Chi-Square Distribution
Claudins - genetics
Cohort Studies
Deoxyribonucleic acid
DNA
DNA sequencing
Enrichment
Excretion
Female
Follow-Up Studies
Gene Frequency
Gene sequencing
Genes
Genetic Predisposition to Disease - genetics
Haplotypes
Humans
Kidney Calculi - genetics
Kidney Calculi - urine
Kidney stones
Kidneys
Male
Medical personnel
Medicine
Middle Aged
Multiplexing
Mutation
Next-generation sequencing
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Risk Factors
Rodents
Sequence Analysis, DNA
Single-nucleotide polymorphism
Urine
Womens health
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Summary:Our study investigated the association of rare allelic variants with extremes of 24-hour urinary calcium excretion because higher urinary calcium excretion is a dominant risk factor for calcium-based kidney stone formation. We resequenced 40 candidate genes potentially related to urinary calcium excretion in individuals from the Nurses' Health Studies I & II and the Health Professionals Follow-up Study. A total of 960 participants were selected based on availability of 24-hour urine collection data and level of urinary calcium excretion (low vs. high). We utilized DNA sample pooling, droplet-based target gene enrichment, multiplexing, and high-throughput sequencing. Approximately 64% of samples (n = 615) showed both successful target enrichment and sequencing data with >20-fold deep coverage. A total of 259 novel allelic variants were identified. None of the rare gene variants (allele frequencies
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0071885