Genome architecture, rearrangements and genomic disorders.
Structural variation in the human genome and its role in disease.
The discovery of submicroscopic copy-number variations (CNVs) present in the authors' genomes has changed dramatically their perspective on DNA structural variation and disease and it is now thought that CNVs encompass more total nucleotides and arise more frequently than SNPs.
Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements
Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes
The analyses of chromosome breakpoints in the proximal short arm of Chromosome 17 (17p) reveal nonallelic homologous recombination (NAHR) as a major mechanism for recurrent rearrangement whereas nonhomologous end-joining (NHEJ) can be responsible for many of the nonrecurrent rearrangements.
Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size
Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity and support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.
Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.
As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.
Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities
It is proposed that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies.
Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype.
The critical region for Potocki-Lupski syndrome is refined to a 1.3-Mb genomic interval that contains the dosage-sensitive RAI1 gene and lends further support for the concept that genomic architecture incites genomic instability.
Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia
Using genome-wide linkage mapping and a positional candidate approach, it is determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a–like 1), are responsible for SIOD.
Periaxin mutations cause recessive Dejerine-Sottas neuropathy.
The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin, and it is hypothesized that mutations in PRX could cause human peripheral myelinopathies.