Research GReP - Genomics of Recurrent Pregnancy Loss

Approximately 70% of all human fertilizations are naturally aborted, with most occurring before the mother knows she is pregnant. Miscarriages that occur later in pregnancy are often due to non-viable genetic variation and this is very likely in the case of Recurrent Pregnancy Losses (RPL).

Numerical and structural chromosomal abnormalities are routinely investigated to understand causes of RPL, while the study of small-size sequence variants that can impact gene function has been neglected, leaving a whole range of possible causes unexplored.

This project will identify variants severely disrupting genes and regulatory functions, therefore incompatible with life, using whole genome sequence of DNA extracted from chorionic villi of miscarriages collected from women with RPL. preSeq_screaning

We are interested in sequencing euploid miscarriages, therefore we do a pre-sequencing screening to exclude aneuploidies and comorbidities. We estimated that 20% of collected samples is euploid. We also find that with current methods it is not possible to make a diagnosis in about 25% of the samples.

We will identify the highly deleterious dominant mutations as well as rare moderately to highly deleterious recessive mutations that constitute the genetic load of human populations and contribute to miscarriage. Participant inclusion criteria (e.g. recurrence, consanguinity, selection of comorbidities) will ensure the prevalence of genetic over environmental causes, and pre-sequencing screening will exclude cases with large chromosomal aberration.

GReP code is shared here git Collaborations

Qasim Ayub, Monash University, Malaysia

Michele Rubini, University of Ferrara

Cesare Furlanello, Fondazione Bruno Kessler

Funding

Merigen Research s.r.l

POR Campania FSE 2014-2020 ASSE III – Ob. Sp. 14

GReP Pipeline