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Systematic analysis of the involvement of DNA tandem repeats in Amyotrophic lateral sclerosisfrom Whole Genome Sequencing data

The C9ORF72 gene repeat expansion is the most frequent cause of amyotrophic lateral sclerosis (ALS). Long repeats alleles in ATXN-1, ATXN-2, and NIPA1 genes are associated to ALS susceptibility. Thus, Tandem Repeat Polymorphisms (TRPs) are good candidates for missing hereditability in ALS, although they were never systematically analyzed because challenging to NGS. The general aim of this study is to perform a systematic analysis of TRPs in ALS by combining NGS and novel bioinformatics tools. TRPs from whole genome sequencing data (WGS, Illumina HiSeq X Ten, avg. coverage 30X, 2x 150 bp length) of a cohort of 70 ALS cases enriched in FALS cases were evaluated by means of two software developed within our consortium and by a literature software (lobSTR) to detect either expansions with a repeat size within the NGS reads sizes (short TRPs), and repeat expansions larger than the NGS reads sizes. The analysis of short tandem repeat expansion for about 600K loci in 70 ALS cases and 300 controls led to the selection of 20 TRPs showing a significant distribution among patients and controls. The validation of these loci by traditional methods revealed a high technical consistency (70%). However, we failed to replicate this data in an independent sample (208 Italian ALS patients and 229 matched controls). For large repeat expansions detection, the analysis of 700K TRPs identified 16 loci with potential very large repeat expansion observed in 1 or 2 of the 70 patients, and whose validation and replication is ongoing.

Abstracts from the 51st European Society of Human Genetics (ESHG) Conference, Milano, 2018

Autori IIT:

Loredana Marialuisa Genovese

Foto di Loredana Marialuisa Genovese

Tipo: Abstract in atti di convegno
Area di disciplina: Computer Science & Engineering

File: s41431-019-0404-7 313.pdf

Attività: Biologia computazionale