ABSTRACT
Bacterial artificial chromosomes [BACs]-on-Beads [BoBs] is one of the novel and rapid technologies that has been a part of recent advances in genomic technologies. BACs-on- Beads technology [Trade Mark] that assists in speedy detection of copy number changes [CNVs] in targeted genomic regions from minimal amount of DNA. We compared this molecular multiplex, bead-based suspension array that is used in prenatal invasive testing, with conventional cytogenetic and G-banded karyotype techniques. We present the initial BoBs analysis data of 4 patients referred to CABRI with congenital malformations. As per the manufacture's information the targeted region covers at least 4-5 bacs for each region. The selected loci represent the relatively common chromosomal syndromes associated with deletions that can be missed by karyotype analysis. The syndromes are known with definable phenotype and deletion as the major means giving rise to the syndrome. In addition to this the BAC's for the common aneuploidies of chromosomes 13, 18, 21, X, and Y are also present. The method not only detected the known trisomy 21 but also identified a deletion on the long arm of chromosome 7 at q11.2 region that represents the Williams - Beuran Syndrome [WBS] critical region in a patient with suspected trisomy 21. BoBs is potentially a very useful first row test for aneuploidy detection because of its lower cost and rapid detection with minimal amount of DNA especially in newborns with suspected congenital malformations. The results suggest that it is a reliable technique to detect common microdeletions that get missed out by conventional chromosomal analysis
ABSTRACT
Array comparative genome hybridization [aCGH] has been a powerful tool that allows a high resolution whole genome analysis of copy number variations and single nucleotide polymorphisms [SNPs] that can reveal submicroscopic deletions, duplications loss of homo or heterozygosity [LOH] and uniparental disomy. We present aCGH analysis data of 4 patients referred with autism that was analyzed using a high density oligo/SNP array with over 1.9 million markers for copy number variations [CNV's] and about 750,000 SNPs [Affymetrix]. After careful evaluation, we found no genomic CNVs that were previously described but noticed several regions with loss of heterzygosity [LOH] in 2 of the 4 patients analyzed. The regions of LOH range from 7Mb to over 29Mb in patient A2 and from over 3Mb to over 63Mb in patient A3. Some of the LOH noticed in these patients are seen associated with genes responsible for causing Autism. The genes noticed have been fully characterized and classified as Autism genes. Patient A2 has only one gene involved [DPP10 [2q14.1]] and patient A3 has 5 genes [MBD5 [2q23.1], SCN1A, SCN2A [2q24.3], KCTD13 [16p11.2] and PAFAH1B1 [17p13.3]]. Several regions of LOH detected in these two patients encompass -101 Mb and 201 Mb of the total genome respectively. The results suggest that it is not related to a specific disorder but involvement of at least gene in the LOH region can raise the possibility of a recessive condition. The importance of LOH and the details of the genes will be discussed