Dataset Information

Allelic frequencies of the hs1.2 enhancer within the immunoglobulin heavy chain region in Dayton, Ohio patients screened for celiac disease with duodenal biopsy.

ABSTRACT: Genetic and environmental factors contribute to the development of celiac disease (CD), but specific genetic predisposing factors remain poorly understood. One candidate is allele 2 of the hs1.2 enhancer within the immunoglobulin heavy chain region. In humans, there are four possible alleles and a previous study of an Italian cohort demonstrated a significantly increased frequency of allele 2 in patients with CD.The purpose of the current study was to determine if a similar association between allele 2 and CD exists in an American population from Dayton, OH.Subjects were screened for CD via esophagogastroduodenoscopy with duodenal biopsy. All biopsies were microscopically scored using a modified Marsh-Oberhuber classification. DNA was isolated from patients' buccal cells for hs1.2 genotype analysis using PCR.Unlike the Italian cohort, allele 2 frequency was not significantly different in patients with histopathologic evidence of CD compared to patients without such evidence. However, our patient population as a whole demonstrated a significantly increased allele 2 frequency when compared to that previously reported within diverse ethnic populations.Since our comparative control patients do not necessarily reflect a healthy control population, an overall increase in allele 2 may reflect an association between allele 2 of the hs1.2 enhancer and a spectrum of gastrointestinal disorders.

SUBMITTER: Liu J

PROVIDER: S-EPMC5511760 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Allelic frequencies of the hs1.2 enhancer within the immunoglobulin heavy chain region in Dayton, Ohio patients screened for celiac disease with duodenal biopsy.

Liu Jing J Law Rebecca A RA Koles Paul G PG Saxe Jonathan C JC Bottomley Michael M Sulentic Courtney E W CEW

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 20170409 8

<h4>Background</h4>Genetic and environmental factors contribute to the development of celiac disease (CD), but specific genetic predisposing factors remain poorly understood. One candidate is allele 2 of the hs1.2 enhancer within the immunoglobulin heavy chain region. In humans, there are four possible alleles and a previous study of an Italian cohort demonstrated a significantly increased frequency of allele 2 in patients with CD.<h4>Aims</h4>The purpose of the current study was to determine if ...[more]

PMID: 28473300

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Project description:The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp). Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype) can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for quantitatively handling regions of copy number variation in other structurally varying and complex loci.

Dataset Information

Allelic frequencies of the hs1.2 enhancer within the immunoglobulin heavy chain region in Dayton, Ohio patients screened for celiac disease with duodenal biopsy.

Publications

Allelic frequencies of the hs1.2 enhancer within the immunoglobulin heavy chain region in Dayton, Ohio patients screened for celiac disease with duodenal biopsy.

Similar Datasets

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