Project description:Neurodevelopmental conditions with a genetic component, such as autism, are a highly heritable heterogeneous group. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex families and autistic traits still warrants investigation. Here, we conducted whole-genome sequencing of 21 highly multiplex autism families, with at least three autistic individuals in each family, to prioritise genes associated with autism. Using a combination of both autistic traits and clinical diagnosis of autism, we identify rare variants in genes associated with autism, and related neurodevelopmental conditions in multiple families. We identify a modest excess of these variants in autistic individuals compared to individuals without an autism diagnosis. Finally, we identify a convergence of the genes identified in molecular pathways related to development and neurogenesis. In sum, our analysis provides initial evidence to demonstrate the value of integrating autism diagnosis and autistic traits to prioritise genes.

| EGAS00001006928 | EGA

SNP genotyping of multiplex autoimmune Addison's families from the UK and Norway

Project description:Multiplex AAD families from the UK and Norway, genotyped on the Affymetrix SNP 6 array

| EGAS00001001237 | EGA

CIDR Whole Exome sequencing of multiplex cleft families

Project description:<p>Building upon our previous linkage and association studies, we will use whole exome sequencing studies of second and third degree affected relatives drawn from multiplex families. Our specific aims are: 1) To conduct whole exome sequencing on affected members (2° and 3° relatives) drawn from multiplex cleft families from a consortium to identify novel genes causing non-syndromic oral clefts; 2) To confirm and test the role of rare variants in these novel genes through confirmatory Sanger sequencing, plus linkage information using additional members available in these multiplex families. This whole exome sequencing approach will combine evidence from linkage studies and large scale sequencing to identify novel genes causing oral clefts in multiplex cleft families. </p>

| phs000459 | dbGaP

Reliable Multiplex Sequencing with Rare Index Mis-Assignment on DNB-Based NGS Platform

Project description:Reliable Multiplex Sequencing with Rare Index Mis-Assignment on DNB-Based NGS Platform

| PRJEB27504 | ENA

Genotyping data for seven patients from three unrelated, consanguineous multiplex families that presented with combined immunodeficiency, and were found to harbour mutations in CARMIL2

Project description:Combined immunodeficiencies are a heterogeneous collection of primary immune disorders that exhibit defects in T cell development or function, along with impaired B cell activity even in light of normal B cell maturation. CARMIL2 (RLTPR) is a protein involved in cytoskeletal organization and cell migration which also plays a role in CD28 co-signaling of T cells. Mutations in this protein have recently been reported to cause a novel primary immunodeficiency disorder with variable phenotypic presentations. Here we deposit genotyping data for seven patients from three unrelated, consanguineous multiplex families that presented with dermatitis, eosophagitis and recurrent skin and chest infections with evidence of combined immunodeficiency. By using this genotyping data to perform autozygome-guided analysis, and coupling it with the results of whole exome sequencing, we uncovered two mutations not previously reported (p.R50T and p.L846Sfs) in CARMIL2.

2018-01-25 | E-MTAB-6440 | biostudies-arrayexpress

Bambusa multiplex

Project description:Bambusa multiplex overview

| PRJNA399780 | ENA