title: The fetal thymus has a unique genomic copy number profile resulting from physiological T cell receptor gene rearrangement.
abstract: Somatic mosaicism, the presence of genetically distinct cells within an organism, has been increasingly associated with human morbidity, ranging from being a cause of rare syndromes to a risk factor for common disorders such as malignancy and cardiovascular disease. Previous studies interrogating the normal prevalence of somatic mosaicism have focused on adults. We here present an estimate of the baseline frequency of somatic mosaic copy number variation (CNV) at the time around birth, by sampling eight different organs from a total of five fetuses and newborns. Overall we find a significantly lower frequency of organ specific (i.e. mosaic) CNVs as compared to adults (p = 0.003; Mann-Whitney U-test). The rate of somatic CNV in adults has been estimated to around 2.2 CNV per organ assayed. In contrast, after stringent filtering, we found no organ-private CNVs in fetuses or newborns with exception of the thymus. This organ exhibited a specific genome profile in the form of deletions resulting from polyclonal T-cell receptor rearrangements. This implies that somatic non-immune related CNVs, if present at birth, are typically confined to very small cell populations within organs.
authors.affiliation: Department of Clinical Genetics, Lund University BMC C13, Lund University, SE 221 84, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Valind
authors.affiliation: Department of Clinical Genetics, Lund University BMC C13, Lund University, SE 221 84, Lund, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Haikal
authors.affiliation: Department of Clinical Genetics, Lund University BMC C13, Lund University, SE 221 84, Lund, Sweden.
authors.forename: M E K
authors.initials: ME
authors.lastname: Klasson
authors.affiliation: Department of Oncology, Lund University University Hospital, SE 221 85, Lund, Sweden.
authors.forename: M C
authors.initials: MC
authors.lastname: Johansson
authors.affiliation: Department of Clinical Genetics, Lund University BMC C13, Lund University, SE 221 84, Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Gullander
authors.affiliation: Department of Clinical Genetics, Skåne Regional and University Laboratories University Hospital, SE 221 85, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Soller
authors.affiliation: Department of Oncology, Lund University University Hospital, SE 221 85, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Baldetorp
authors.affiliation: Department of Clinical Genetics, Lund University BMC C13, Lund University, SE 221 84, Lund, Sweden.|Department of Pathology, Skåne Regional and University Laboratories University Hospital, SE 221 85, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Gisselsson
mesh_terms: D056915:DNA Copy Number Variations; D015329:Gene Rearrangement, T-Lymphocyte; D019672:Genes, T-Cell Receptor; D015894:Genome, Human; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism; D009928:Organ Specificity; D013950:Thymus Gland / Q000196:embryology*