Probable germline gene sequences from thousands of aligned mature Ab sequences are inferred using simple computational matching to known V(D)J genes. Comparison of the germline to mature sequences in a structural region-dependent fashion allows insights into the methods that nature uses to mature Abs during the somatic hypermutation process. Four factors determine the residue type mutation patt...

Most studies of mutation rates implicitly assume that they remain constant throughout development of the germline. However, researchers recently used a novel statistical framework to reveal that mutation rates differ dramatically during sperm development in Drosophila melanogaster. Here a general framework is described for the inference of germline mutation patterns, generated from either mutat...

Carney-Stratakis Syndrome (CSS), first described in 2002 [1], encompasses Gastrointestinal Stromal Tumors (GISTs) and Paragangliomas (PGLs) has autosomal dominant inheritance with incomplete penetrance [2]. Germline mutations of Succinate Dehydrogenase (SDH) complex subunits consequent SDH functional deficiency have been identified as responsible for CSS [3]. Here, we present a case new mutatio...

BACKGROUND Familial adenomatous polyposis (FAP) patients develop various extracolonic lesions; however, the relationship between germline mutation of the APC gene and extracolonic manifestations is mostly unknown. To examine the genotype-phenotype relationship, we compared the APC mutation and clinical data. METHODS Germline mutations from codon 157 to 1465 of the APC gene were identified in ...

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer susceptibility syndrome characterized by early-onset diffuse gastric cancer (DGC) and lobular breast cancer. E-cadherin (CDH1) heterozygous germline mutations and deletions are found in 40% of families. Independent of CDH1 alterations, most HDGC tumours display mislocalized or absent E-cadherin immunoexpression, therefore ...

Breast cancers arising in women with and without a germline mutation in the BRCA1 or BRCA2 gene display different histological features, which suggests unique mechanisms of molecular pathogenesis: We used a molecular pathological analysis to define the genetic abnormalities relevant to these specific pathogeneses. Tumor material was studied from 40 women with breast cancer diagnosed before 40 y...

BACKGROUND Head and neck paraganglioma (PGL) are benign tumors that can cause important direct or surgery induced morbidity. Almost all familial and 11-29% of sporadic PGL are caused by inactivating germline mutations in succinate dehydrogenase (SDH) genes. Our aim was to screen for such mutations and to evaluate clinical parameters as predictors of germline mutation. METHODS Seventy-four PGL...

2 Letter Mendez et al. 1 recently report the identification of a Y chromosome lineage from an African American that is an outgroup to all other known Y haplotypes, and report a time to most recent common ancestor, TMRCA, for human Y lineages that is substantially longer than any previous estimate 2-4. The identification of a novel Y haplotype is always exciting, and this haplotype, in particula...

PURPOSE Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain. EXPERIMENTAL DESIGN Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic lo...

Dear Editor, Lynch syndrome (LS) is caused by a germline mutation in one of the mismatch repair (MMR) genes. Individuals with LS have an increased risk developing colorectal and many other tumours including skin tumours.1 Sebaceous neoplasms keratoacanthomas are associated LS, also known as Muir-Torre syndrome. For cutaneous squamous cell carcinoma (SCC), association has been suggested.