Replacement of the myotonic dystrophy type 1 CTG repeat with “non-CTG repeat” insertions in specific tissues

One of the most mutation-prone sequences is the variable number of repeating DNAs at the myotonic dystrophy (DM1) gene, causing muscular dystrophy.  In DM1 individuals the mutant gene has an expansion of a repeated DNA sequence CTG CTG CTG to hundreds or thousands of repeats.  We report a new kind of mutation at the DM1 […]

Read More…

Chromosomes do it by halves

Extra/missing chromosomes are the leading cause of mental retardation, pregnancy loss and IVF failure.  Most arise in the egg however the mechanism by which errors occur is under debate.  Normally, each chromosome of a pair migrates to opposite cell poles before cell division (disjunction); the textbook dogma suggests that errors occur when two chromosomes migrate […]

Read More…

Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour

Testicular cancer is the most common cancer affecting young men and, like many other adult-onset cancers, multiple-case families do occur.  The genetic architecture of familial and sporadic cancers often differs, with rare, highly-penetrant mutations causing the former, and multiple common low-penetrance genetic variants underlying the latter. The study by Kratz and colleagues investigated familial testicular […]

Read More…

Accounting for genetic heterogeneity in homozygosity mapping: application to Mendelian susceptibility to mycobacterial disease

Mendelian diseases for which a single mutation can be identified in a given patient may be characterized by genetic heterogeneity if different patients bear mutations in several different genes. We demonstrate through simulations that a statistical approach (called S/EmpP) can more easily identify chromosomal regions likely to bear mutations in the context of genetic heterogeneity […]

Read More…

The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells

Cystinosis is a debilitating, potentially fatal, inherited metabolic disease. The major genetic defect is a large (57-kb) deletion on chromosome 17 that removes the majority of a cystine transporter gene (CTNS). To find other genes that may also play a role in cystinosis, we collected blood cells from cystinosis families and examined the level of […]

Read More…

Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

The manuscript by Girotto et al. describes the discovery of new genes and pathways that underlie normal hearing function. The strategy applied combines the power of studying isolated populations with a) a general screening of hearing function, b) high-throughput SNP analysis, c) Genome Wide Association Studies (GWAS), and d) up-to-date in silico pathways construction. Data […]

Read More…

Unexpected findings in cancer predisposition genes detected by array comparative genomic hybridisation: what are the issues?

Developmental delay, learning difficulties, behavioural abnormalities and birth defects are often caused by gains or losses of genetic material.  Array comparative genomic hybridisation (aCGH) is a new technology which is more sensitive than previous technologies, and therefore detects these causative changes and provides a diagnosis in more patients than was previously possible.  However, a(CGH) may […]

Read More…