Deciphering copy number variation in susceptibility to testicular germ cell tumour (360G-Wellcome-207311_Z_17_Z)

Testicular germ cell tumour (TGCT) has a strong inherited basis with brothers of cases having a 6—10 fold increased risk of disease and heritability of > 45%. Whilst GWAS studies have identified > 25 loci associated with disease, the underlying causative variants and mechanisms for conferring susceptibility to the disease are poorly understood. Furthermore, whilst recent whole exome analysis had implicated rare variants in genes related to microtubule and ciliary function in familial TGCT, these rare variants only account for a modest proportion of disease heritability. To date there has been no exposition of the role of copy number variation in susceptibility to TGCT and it is plausible that copy number variants may contribute to the "missing heritability" of TGCT. Furthermore, identification of copy number variants implicated in TGCT susceptibility may be informative with regard to highlighting novel TGCT susceptibility genes located within the regions of copy number variation. In this project I shall deploy copy number-calling algorithms on (i) SNP array data on 7319 TGCT cases and 23082 controls and (ii) whole exome sequencing data on an overlapping set of 962 TGCT cases and 1644 controls.