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
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.
Eur J Hum Genet. 2014 Nov 26;
Authors: Jalkh N, Sahbatou M, Chouery E, Megarbane A, Leutennegger AL, Serre JL
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]
Erratum to: high-resolution SNP array analysis of patients with developmental disorder and normal array CGH result.
BMC Med Genet. 2014;15(1):124
Authors: Siggberg L, Ala-Mello S, Linnankivi T, Avela K, Scheinin I, Kristiansson K, Lahermo P, Hietala M, Metsähonkala L, Kuusinen E, Laaksonen M, Saarela J, Knuutila S
PMID: 25409779 [PubMed - as supplied by publisher]
Three gangliogliomas: Results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.
Neuropathology. 2014 Nov 6;
Authors: Xu LX, Holland H, Kirsten H, Ahnert P, Krupp W, Bauer M, Schober R, Mueller W, Fritzsch D, Meixensberger J, Koschny R
According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas.
PMID: 25376146 [PubMed - as supplied by publisher]