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Genome-wide patterns of genetic variation in individuals with autism spectrum disorders from Croatia

Genome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis. As a first step in the genetic analysis of ASD in Croatia, we characterized genetic variation in a sample of 103 subjects with ASD and 203 control individuals, whom were genotyped using the Illumina HumanHap550 BeadChip. Combining the Croatian cohorts with several previously published populations in the FastME analysis (an alternative to Neighbor Joining) revealed that Croatian subjects cluster, as expected, with Southern Europeans ; in addition, individuals from the same geographic region within Europe cluster together. Whereas Croatian subjects could be separated from a sample of healthy control subjects of European origin from North America, Croatian ASD cases and controls are well mixed. A comparison of runs of homozygosity indicated that the number and the median length of regions of homozygosity are higher for ASD subjects than for controls (p=6×10-3). Furthermore, analysis of copy number variants demonstrated higher frequency of large chromosomal rearrangements (> 2Mb) in ASD cases than in ethnically matched control subjects (p=0.019). Our findings illustrate the remarkable utility of high-density genotype data for subjects from a limited geographic area in dissecting genetic heterogeneity with respect to population and disease related variation.

autism spectrum disorders; copy number variation; runns of homozygosity; genome-wide scan

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