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Eur J Hum Genet. 2015 May;23(5):663-71. doi: 10.1038/ejhg.2014.153. Epub 2014 Aug 13.

Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility.

Author information

1
Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
2
Division of Medical Genetics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
3
Division of General Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
4
Molecular Biology Center GENETAQ, Málaga, Spain.
5
Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
6
Children's Hospital Central California, Madera, CA, USA.
7
Rady Children's Hospital, San Diego, CA, USA.
8
Department of Pediatrics, Section of Genetics, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
9
Center for Computational Science, University of Miami, Miami, FL, USA.

Abstract

Copy neutral segments with allelic homozygosity, also known as regions of homozygosity (ROHs), are frequently identified in cases interrogated by oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence of ROHs may be because of parental relatedness, chromosomal recombination or rearrangements and provides important clues regarding ancestral homozygosity, consanguinity or uniparental disomy. In this study of 14 574 consecutive cases, 832 (6%) were found to harbor one or more ROHs over 10 Mb, of which 651 cases (78%) had multiple ROHs, likely because of identity by descent (IBD), and 181 cases (22%) with ROHs involving a single chromosome. Parental relatedness was predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy (isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5 cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive disorders were confirmed in seven of nine cases from eight families because of the finding of suspected gene within a ROH. This study demonstrates that ROHs are much more frequent than previously recognized and often reflect parental relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases.

PMID:
25118026
PMCID:
PMC4402629
DOI:
10.1038/ejhg.2014.153
[Indexed for MEDLINE]
Free PMC Article

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