title: Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility.
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.
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Jia-Chi
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Ross
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Loretta W
authors.initials: LW
authors.lastname: Mahon
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Renius
authors.initials: R
authors.lastname: Owen
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Morteza
authors.initials: M
authors.lastname: Hemmat
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Boris T
authors.initials: BT
authors.lastname: Wang
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Naggar
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kopita
authors.affiliation: Division of Medical Genetics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Randolph
authors.affiliation: Division of General Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Chase
authors.affiliation: Molecular Biology Center GENETAQ, Málaga, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Matas Aguilera
authors.affiliation: Molecular Biology Center GENETAQ, Málaga, Spain.
authors.forename: Juan López
authors.initials: JL
authors.lastname: Siles
authors.affiliation: Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Church
authors.affiliation: Children's Hospital Central California, Madera, CA, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hauser
authors.affiliation: Children's Hospital Central California, Madera, CA, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Shen
authors.affiliation: Rady Children's Hospital, San Diego, CA, USA.
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Section of Genetics, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Wierenga
authors.affiliation: Center for Computational Science, University of Miami, Miami, FL, USA.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Haddadin
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Fatih Z
authors.initials: FZ
authors.lastname: Boyar
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Anguiano
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Strom
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003241:Consanguinity; D005190:Family; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult