Genome-wide analyses demonstrate novel loci that predispose to drusen formation.

Purpose: To test whether genes for drusen formation are independent of age-related macular degeneration (AMD) pathogenesis.

Methods: A genome-wide model-free linkage analysis was performed, using two semiquantitative drusen traits, size and type, on two sets of data: (1) 325 individuals (225 sib pairs) from the Beaver Dam Eye Study (BDES), and (2) 297 individuals (346 sib pairs) from the Family Age Related Maculopathy Study (FARMS). Apolipoprotein E (APOE) genotypes were used as a covariate in a multipoint sibpair analysis.

Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers linked to a quantitative measure of cortical opacity.

The fa leptin receptor mutation and the heritability of respiratory frequency in a Brown Norway and Zucker intercross.

We sought to determine whether the fa (leptin receptor) mutation was a major determinant of the putative obesity effects on respiratory frequency in an intercross between the Brown Norway (low breathing frequency, nonobese strain) and the Zucker (moderately high breathing frequency, with the fa mutation) strains. The hypothesis was that rats bearing one (heterozygote) or two (homozygote) alleles of the Glu296Pro point mutation (fa) would have a uniformly high respiratory frequency in the second filial (F2) generation, compared with wild-type animals. In addition to breathing frequency, tidal volume and minute ventilation were assessed during baseline, acute hypoxic (10% O2-0% CO2-balance nitrogen), hypercapnic (93% O2-7% CO2), hyperoxic (100% O2-0% CO2), and combined (10% O2-3% CO2-balance nitrogen) challenges in fa homozygote (fa/fa; n = 24), fa heterozygote (fa/wt; n = 33), and wild-type (wt/wt; n = 19) animals.

Pleiotropic effects of a chromosome 3 locus on speech-sound disorder and reading.

Speech-sound disorder (SSD) is a complex behavioral disorder characterized by speech-sound production errors associated with deficits in articulation, phonological processes, and cognitive linguistic processes. SSD is prevalent in childhood and is comorbid with disorders of language, spelling, and reading disability, or dyslexia. Previous research suggests that developmental problems in domains associated with speech and language acquisition place a child at risk for dyslexia.

Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration.

To examine the genetic basis of age-related macular degeneration (ARMD), a degenerative disease of the retinal pigment epithelium and neurosensory retina, we conducted a genomewide scan in 34 extended families (297 individuals, 349 sib pairs) ascertained through index cases with neovascular disease or geographic atrophy. Family and medical history was obtained from index cases and family members. Fundus photographs were taken of all participating family members, and these were graded for severity by use of a quantitative scale.