Nature Medicine | ResourceNature Medicine / Published online January 2015
Whole lot of unproven presumptions and assumptions going on, and these results do not support those assumptions!
Whole-genome sequencing of quartet families with autism spectrum disorder
- (There are scads of authors / affiliation on original page)
- Autism spectrum disorder (ASD) is genetically heterogeneous, with +evidence for hundreds of susceptibility loci. (Heterogeneous: Genetic heterogeneity is a phenomenon in which a single phenotype or genetic disorder may be caused by any one of a multiple number of alleles or non-allele (locus) mutations. This is in contrast to pleiotropy, where a single gene may cause multiple phenotypic expressions or disorders. + Note that the ASSUMPTION IS that ASD is a “genetic disorder” – this has not been proven. This study is a panoramic approach: try to find any genetic linkage between ASD individuals in two “types” of families.) Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics. (We got bupkis!)