לוח שנה משולב

Observations on all scales point to a gap in our understanding of gravitation; from the Pioneer anomaly in the solar system, through the shape of galaxy rotation curves and the amount of gravitational lensing by galaxy clusters, to the accelerated expansion of the universe. This observed discrepancy between the dynamics and the distribution of the visible matter in the universe is usually ascribed to dark matter and dark energy. However, it is possible that both dark matter and dark energy are manifestations of a theory of gravity different than General Relativity. One such theory is TeVeS, suggested by Bekenstein in 2004. I will present several results on the match up of TeVeS with observations. Surprisingly, its PPN parameters show it to be indiscernible from GR in the solar system; however, its gravitational waves exhibit an unusual behavior, which can be traced back to the theory's MOND origin.

BACKGROUND: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease.

METHODS: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members.

RESULTS: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome.

CONCLUSIONS: 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.