Study of split hand/foot malformation with genomic techniques and bioinformatic approaches

Split hand/foot malformation is a rare genetic disorder characterized by missing middle digits in hand and foot. Genetic diseases that inherited according to Mendelien autosomal recessive (AR) model have a higher prevelance in regions with higher consanguineous marriages. Many of the genetic disorders with AR inheritance has been identified with next generation sequencing and array technologies. In this study total of 41 individuals from 4 families with consanguineous marriages were studied using different combinations of SNP array, homozygous mapping, linkage analysis, and exome sequencing methods to identify pathogenic candidate variants. Analyses performend on MA134 family revealed NM_003394.4:c.994C>G:p.Arg332Gly pathogenic variant in SHFM related WNT10B gene. Analyses performed on MA136 family revealed NM_003394.4:c.343C>T:p.Arg115Ter pathogenic also on WNT10B gene. Analyses performed on MA154 family showed CNV gain on SHFM related 10q24 region. No pathogenic variants or genomic regions have been discovered by analyses performed on MA135. Alongside analyses of 4 families, two software has been developed. First one is to automatizing pipelines used in next generation sequencing and second one for annotating VCF format after raw data analyses as well as filtering variants and in family analyses. Links: https://pypi.org/project/seq-pigeon/ and https://pypi.org/project/seq-dove/ Key Words: SHFM, Developmental Genetics, Bioinformatics, NGS, SNP array