De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child with mixed phenotypes.

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De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child with mixed phenotypes.

J Genet. 2014 Dec;93(3):869-73

Authors: Córdova-Fletes C, Sáinz-González E, Avendaño-Gálvez RI, Ramírez-Velazco A, Rivera H, Ortiz-López R, Arámbula-Meraz E, Picos-Cárdenas VJ

PMID: 25572250 [PubMed - in process]

SNP arrays: comparing diagnostic yields for four platforms in children with developmental delay.

SNP arrays: comparing diagnostic yields for four platforms in children with developmental delay.

BMC Med Genomics. 2014 Dec 24;7(1):2

Authors: D Amours G, Langlois M, Mathonnet G, Fetni R, Nizard S, Srour M, Tihy F, S Phillips M, L Michaud J, Lemyre E

Abstract
BackgroundMolecular karyotyping is now the first-tier genetic test for patients affected with unexplained intellectual disability (ID) and/or multiple congenital anomalies (MCA), since it identifies a pathogenic copy number variation (CNV) in 10-14% of them. High-resolution microarrays combining molecular karyotyping and single nucleotide polymorphism (SNP) genotyping were recently introduced to the market. In addition to identifying CNVs, these platforms detect loss of heterozygosity (LOH), which can indicate the presence of a homozygous mutation or of uniparental disomy. Since these abnormalities can be associated with ID and/or MCA, their detection is of particular interest for patients whose phenotype remains unexplained. However, the diagnostic yield obtained with these platforms is not confirmed, and the real clinical value of LOH detection has not yet been established.MethodsWe selected 21 children affected with ID, with or without congenital malformations, for whom standard genetic analyses had failed to provide a diagnosis. We performed high-resolution SNP array analysis with four platforms (Affymetrix Genome-Wide Human SNP Array 6.0, Affymetrix Cytogenetics Whole-Genome 2.7 M array, Illumina HumanOmni1-Quad BeadChip, and Illumina HumanCytoSNP-12 DNA Analysis BeadChip) on whole-blood samples obtained from the children and their parents to detect pathogenic CNVs and LOHs, and compared the results with those obtained on a moderate resolution array-based comparative genomic hybridization platform (NimbleGen CGX-12 Cytogenetics Array), already in use in the clinical setting.ResultsWe identified a total of four pathogenic CNVs in three patients, and all arrays successfully detected them. With the SNP arrays, we also identified a LOH containing a gene associated with a recessive disorder consistent with the patient¿s phenotype (i.e., an informative LOH) in four children (including two siblings). A homozygous mutation within the informative LOH was found in three of these patients. Therefore, we were able to increase the diagnostic yield from 14.3% to 28.6% as a result of the information provided by LOHs.ConclusionsThis study shows the clinical usefulness of SNP arrays in children with ID, since they successfully detect pathogenic CNVs, but also identify informative LOHs that can lead to the diagnosis of a recessive disorder. It also highlights some of the challenges associated with the use of SNP arrays in a clinical laboratory.

PMID: 25539807 [PubMed - as supplied by publisher]

Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies.

Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies.

Hum Mutat. 2014 Dec 15;

Authors: Van Opstal D, de Vries F, Govaerts L, Boter M, Lont D, van Veen S, Joosten M, Diderich K, Galjaard RJ, Srebniak MI

Abstract
We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared to rapid aneuploidy detection (RAD) and karyotyping. 1330 prenatal samples were investigated with a 0.5 Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1330) of the cases pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age or screening related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1330) for a (sub)microscopic abnormality associated with an early-onset often severe disease, 1:222 (6/1330) for a submicroscopic aberration causing an early-onset disease, 1:74 (18/1330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1330) for a late-onset disorder (HNPP in all 3 cases). These risk figures are important for adequate pre-test counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe that if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication. This article is protected by copyright. All rights reserved.

PMID: 25504762 [PubMed - as supplied by publisher]

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays.

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays.

Eur J Hum Genet. 2014 Nov 26;

Authors: Jalkh N, Sahbatou M, Chouery E, Megarbane A, Leutennegger AL, Serre JL

Abstract
Consanguineous marriages have been widely practiced in several global communities with varying rates depending on religion, culture, and geography. In consanguineous marriages, parents pass to their children autozygous segments known as homozygous by descent segments. In this study, single-nucleotide polymorphisms were analyzed in 165 unrelated Lebanese people from Greek Orthodox, Maronite, Shiite and Sunni communities. Runs of homozygosity, total inbreeding levels, remote consanguinity, and population admixture and structure were estimated. The inbreeding coefficient value was estimated to be 1.61% in offspring of unrelated parents over three generations and 8.33% in offspring of first cousins. From these values, remote consanguinity values, resulting from genetic drift or recurrent consanguineous unions, were estimated in offspring of unrelated and first-cousin parents to be 0.61 and 1.2%, respectively. This remote consanguinity value suggests that for any unrelated marriages in Lebanon, the mates could be related as third cousins or as second cousins once removed. Under the assumption that 25% of marriages occur between first cousins, the mean inbreeding value of 2.3% may explain the increased incidence of recessive disease in offspring. Our analysis reveals a common ancestral population in the four Lebanese communities we studied.European Journal of Human Genetics advance online publication, 26 November 2014; doi:10.1038/ejhg.2014.246.

PMID: 25424710 [PubMed - as supplied by publisher]

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