The human body is formed by trillions of individual cells. These cells work together with remarkable precision, first forming an adult organism out of a single fertilized egg, and then keeping the organism alive and functional for decades. To achieve this precision, one would assume that each individual cell reacts in a reliable, reproducible way to a given input, faithfully executing the requi...

BACKGROUND Essential tremor (ET) is often familial and phenotypic features may be shared within families. Cranial (neck, voice, and jaw) tremor is an important feature of ET. We examined whether cranial tremor aggregates in ET families, after controlling for other factors (age, tremor severity, and duration). METHODS Among ET probands and relatives enrolled in a genetic study at Columbia Univ...

Linkage disequilibrium (LD) plays a central role in current and proposed methods for mapping complex disease genes. LD-based methods work best when there is a single susceptibility allele at any given disease locus, and generally perform very poorly if there is substantial allelic heterogeneity. The extent of allelic heterogeneity at typical complex disease loci is not yet known, but prediction...

Strong evidence suggests that rare mutations of severe effect are responsible for a substantial portion of complex human disease. Evolutionary forces generate vast genetic heterogeneity in human illness by introducing many new variants in each generation. Current sequencing technologies offer the possibility of finding rare disease-causing mutations and the genes that harbor them.

An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile cond...

Certain skeletal dysplasias represent excellent examples of genetic heterogeneity. Clinical recognition of their individual characteristics is a fundamental prerequisite for an understanding of their pathogenetic mechanisms and for the identification of their basic molecular defects.

Considerable clinical variability occurs in adult Gaucher disease type I and three main subtypes may be delineated: a very mild form, a severe form, and a moderate form which itself presents various clinical manifestations. A study based on 25 families from our clinic and a review of published reports showed that when both parents were heterozygous and more than one child was affected with Gauc...

Progress towards the understanding of the molecular basis of US has been substantial. Nine different loci have been found to be responsible and two have had the specific gene identified. This information is expected to lay the foundation for the eventual development of new treatment strategies. Usher syndrome is the combined loss of both of humans most important two senses and a better understa...

During the last few years a quiet revolution has been taking place in our ideas about the genetical basis of inherited disease. One way in which this has been manifested is by the increasing use in the literature of the term 'genetic heterogeneity', a term which is usually meant to imply that the same or very similar clinical syndromes may be produced by a number of quite different gene mutatio...

Neurology 2012;79:619–620 Parkinson disease (PD) is considered a sporadic neurodegenerative disorder, though genetic factors are frequently involved in its etiology. That some familial presentations of PD have been associated with different mutated genes suggests that some genetic variants can also modulate the risk for “nonfamilial” presentation of PD. The hypothesis-free genomewide associatio...