Universität zu Köln

Dron, Jacqueline S., Wang, Jian, Berberich, Amanda J., Iacocca, Michael A., Cao, Henian, Yang, Ping, Knoll, Joan, Tremblay, Karine, Brisson, Diane, Netzer, Christian, Gouni-Berthold, Ioanna, Gaudet, Daniel and Hegele, Robert A. (2018). Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia. J. Lipid Res., 59 (8). S. 1529 - 1536. ROCKVILLE: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1539-7262

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Abstract

Copy-number variations (CNVs) have been studied in the context of familial hypercholesterolemia but have not yet been evaluated in patients with extreme levels of HDL cholesterol. We evaluated targeted, next-generation sequencing data from patients with very low levels of HDL cholesterol (i.e., hypoalphalipoproteinemia) with the VarSeq-CNV (R) caller algorithm to screen for CNVs that disrupted the ABCA1, LCAT, or APOA1 genes. In four individuals, we found three unique deletions in ABCA1: a heterozygous deletion of exon 4, a heterozygous deletion that spanned exons 8 to 31, and a heterozygous deletion of the entire ABCA1 gene. Breakpoints were identified with Sanger sequencing, and the full-gene deletion was confirmed by using exome sequencing and the Affymetrix CytoScan HD array. Previously, large-scale deletions in candidate HDL genes had not been associated with hypoalphalipoproteinemia; our findings indicate that CNVs in ABCA1 may be a previously unappreciated genetic determinant of low levels of HDL cholesterol. By coupling bioinformatic analyses with next-generation sequencing data, we can successfully assess the spectrum of genetic determinants of many dyslipidemias, including hypoalphalipoproteinemia.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dron, Jacqueline S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Jian UNSPECIFIED UNSPECIFIED UNSPECIFIED Berberich, Amanda J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Iacocca, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cao, Henian UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Ping UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoll, Joan UNSPECIFIED UNSPECIFIED UNSPECIFIED Tremblay, Karine UNSPECIFIED UNSPECIFIED UNSPECIFIED Brisson, Diane UNSPECIFIED UNSPECIFIED UNSPECIFIED Netzer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaudet, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hegele, Robert A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-177282
DOI:	10.1194/jlr.P086280
Journal or Publication Title:	J. Lipid Res.
Volume:	59
Number:	8
Page Range:	S. 1529 - 1536
Date:	2018
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1539-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY NUMBER VARIATION; FAMILIAL HDL DEFICIENCY; CASSETTE TRANSPORTER 1; HUMAN GENOME; CHOLESTEROL EFFLUX; TANGIER-DISEASE; STRUCTURAL VARIATION; MUTATIONS; BINDING; DISORDERS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17728