Exploring germline and somatic mutagenesis in the extended family with germline pathogenic variant in POLD1

This study aimed to estimate the influence of POLD1 L474P on somatic and germline mutagenesis. We studied the mutation rate and spectra in germline and soma in an extended family harboring the POLD1 c.1421T>C p.(Leu474Pro) pathogenic variant. The study includes WGS data for DNA extracted from blood, fibroblasts or buccal swabs from the 16 family members, from DNA obtained single-cell derived colonies obtained from immortalized fibroblasts for 8 of 16 family members and from the same single-cell derived immortalized fibroblasts after approximately 40 passages for 6 out of 8 family members. Additionaly, study includes WXS sequencing for 1 tumor FFPE sample and adjacent normal tissue from the individual from one family member.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Samples
EGAD00001009281	This dataset includes WXS sequencing for 1 tumor FFPE sample and adjacent normal tissue from the individual from one family member.	2
EGAD00001009282	The study includes WGS data for DNA extracted from blood, fibroblasts or buccal swabs from sixteen family members, who represent four sub-families, each including two parents and one to three children, comprising a total of eight offspring. In two sub-families POLD1 L474P was carried by the father; in one sub-family, by the mother; and in the other sub-family, both parents had wild-type POLD1.	16
EGAD00001009283	This dataset contains WGS for fibroblasts colonies obtained from carriers and non-carriers of germline POLD1 L474P. Data for single-cell colonies obtained from immortalized fibroblasts are present for eight out of 16 family members (six carriers and two non-carriers). Sequences obtained for colonies after approximately 40 passages also present for six out of these eight colonies (four carriers and 2 non-carriers). Samples marked with "_F2" and "_F3" represent sequences of single cell-derived colonies and colonies after ~40 passages correspondingly.	14

Publications	Citations
Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells. Andrianova MA, Seplyarskiy VB, Terradas M, Sánchez-Heras AB, Mur P, Soto JL, Aiza G, Borràs E, Kondrashov FA, Kondrashov AS, Bazykin GA, Valle L. Eur J Hum Genet 32: 2024 837-845	1