Universität zu Köln

Gillentine, Madelyn A., Lupo, Philip J., Stankiewicz, Pawel and Schaaf, Christian P. (2018). An estimation of the prevalence of genomic disorders using chromosomal microarray data. J. Hum. Genet., 63 (7). S. 795 - 802. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1435-232X

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Abstract

Multiple genomic disorders result from recurrent deletions or duplications between low copy repeat (LCR) clusters, mediated by nonallelic homologous recombination. These copy number variants (CNVs) often exhibit variable expressivity and/or incomplete penetrance. However, the population prevalence of many genomic disorders has not been estimated accurately. A subset of genomic disorders similarly characterized by CNVs between LCRs have been studied epidemiologically, including Williams-Beuren syndrome (7q11.23), Smith-Magenis syndrome (17p11.2), velocardiofacial syndrome (22q11.21), Prader-Willi/Angelman syndromes (15q11.2q12), 17q12 deletion syndrome, and Charcot-MarieTooth neuropathy type 1/hereditary neuropathy with liability to pressure palsy (PMP22, 17q11.2). We have generated a method to estimate prevalence of highly penetrant genomic disorders by (1) leveraging epidemiological data for genomic disorders with previously reported prevalence estimates, (2) obtaining chromosomal microarray data on genomic disorders from a large medical genetics clinic; and (3) utilizing these in a linear regression model to determine the prevalence of this syndromic copy number change among the general population. Using our algorithm, the prevalence for five clinically relevant recurrent genomic disorders: 1q21.1 microdeletion (1/6882 live births) and microduplication syndromes (1/6309), 15q13.3 microdeletion syndrome (1/5525), and 16p11.2 microdeletion (1/3021) and microduplication syndromes (1/4216), were determined. These findings will inform epidemiological strategies for evaluating those conditions, and our method may be useful to evaluate the prevalence of other highly penetrant genomic disorders.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gillentine, Madelyn A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lupo, Philip J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stankiewicz, Pawel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaaf, Christian P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-182060
DOI:	10.1038/s10038-018-0451-x
Journal or Publication Title:	J. Hum. Genet.
Volume:	63
Number:	7
Page Range:	S. 795 - 802
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1435-232X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY-NUMBER VARIATIONS; 15Q13.3 MICRODELETION; PHENOTYPES; DUPLICATIONS; INDIVIDUALS; VARIANT Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18206