Hereditary deafness: molecular genetics

This article outlines recent advances in explaining hereditary deafness in molecular terms, focusing on isolated (i.e. nonsyndromic) hearing loss. The number of genes identified (36 to date) is growing rapidly. However, difficulties inherent in genetic linkage analysis, coupled with the possible involvement of environmental causes, have so far prevented the characterization of the main genes causative or predisposing to the late-onset forms of deafness.     

Fractionating the musical mind: insights from congenital amusia

Music, like language, is acquired effortlessly in early life and fulfils a multitude of social, cultural and emotional functions. However, those with a disorder recently termed 'congenital amusia' (CA) fail to recognise common tunes from their culture, do not hear when notes are 'out of tune' and sometimes report that music sounds like a 'din' or 'banging'. The core deficit appears to be a problem in discriminating pitch direction, a building block for the representation of melodic contour. Familial studies suggest the disorder is heritable and associated with structural differences in temporal and frontal cortices. The disorder provides a window onto the neuro-cognitive architecture of musical processing, and the possible etiologies of disordered development.     

The mechanism of speech processing in congenital amusia: evidence from Mandarin speakers

Congenital amusia is a neuro-developmental disorder of pitch perception that causes severe problems with music processing but only subtle difficulties in speech processing. This study investigated speech processing in a group of Mandarin speakers with congenital amusia. Thirteen Mandarin amusics and thirteen matched controls participated in a set of tone and intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on word discrimination in natural speech and their gliding tone analogs. They also performed worse than controls on discriminating gliding tone sequences derived from statements and questions, and showed elevated thresholds for pitch change detection and pitch direction discrimination. However, they performed as well as controls on word identification, and on statement-question identification and discrimination in natural speech. Overall, tasks that involved multiple acoustic cues to communicative meaning were not impacted by amusia. Only when the tasks relied mainly on pitch sensitivity did amusics show impaired performance compared to controls. These findings help explain why amusia only affects speech processing in subtle ways. Further studies on a larger sample of Mandarin amusics and on amusics of other language backgrounds are needed to consolidate these results.     

The evolutionary genetics of adaptation: a simulation study

It is now clear that the genetic basis of adaptation does not resemble that assumed by the infinitesimal model. Instead, adaptation often involves a modest number of factors of large effect and a greater number of factors of smaller effect. After reviewing relevant experimental studies, I consider recent theoretical attempts to predict the genetic architecture of adaptation from first principles. In particular, I review the history of work on Fisher's geometric model of adaptation, including recent studies which suggest that adaptation should be characterized by exponential distributions of gene effects. I also present the results of new simulation studies that test the robustness of this finding. I explore the effects of changes in the distribution of mutational effects (absolute versus relative) as well as in the nature of the character studied (total phenotypic effect versus single characters). The results show that adaptation towards a fixed optimum is generally characterized by an exponential effects trend.     

On the genetics of prelingual deafness.

In view of the many discordant findings in previous studies regarding the genetics of prelingual deafness, family data (133 nuclear families and 25 pedigrees) were gathered from India. Analysis of these data has revealed that the defect is primarily genetic, which is in agreement with earlier findings. Segregation analysis was performed to compare various autosomal diallelic one-locus and multilocus models. Our analysis revealed that the most parsimonious model for prelingual deafness is that it is controlled by recessive genes at a pair of unlinked diallelic autosomal loci. Individuals are affected if and only if they are recessive homozygous at both loci. The likelihood of the present data under this two-locus multiple recessive homozygosis model is at least 10(8) times higher than that of the one-locus models that were examined in previous studies. This model is also the best-fitting model among other plausible two-locus models.     

Linkage of congenital recessive deafness (gene DFNB10) to chromosome 21q22.3.

Deafness is a heterogeneous trait affecting approximately 1/1,000 newborns. Genetic linkage studies have already implicated more than a dozen distinct loci causing deafness. We conducted a genome search for linkage in a large Palestinian family segregating an autosomal recessive form of nonsyndromic deafness. Our results indicate that in this family the defective gene, DFNB10, is located in a 12-cM region near the telomere of chromosome 21. This genetic distance corresponds to <2.4 Mbp. Five marker loci typed from this region gave maximum LOD scores > or = to 3. Homozygosity of marker alleles was evident for only the most telomeric marker, D21S1259, suggesting that DFNB10 is closest to this locus. To our knowledge, this is the first evidence, at this location, for a gene that is involved in the development or maintenance of hearing. As candidate genes at these and other deafness loci are isolated and characterized, their roles in hearing will be revealed and may lead to development of mechanisms to prevent deafness.     

Congenital amusia: a disorder of fine-grained pitch discrimination.

We report the first documented case of congenital amusia. This disorder refers to a musical disability that cannot be explained by prior brain lesion, hearing loss, cognitive deficits, socioaffective disturbance, or lack of environmental stimulation. This musical impairment is diagnosed in a middle-aged woman, hereafter referred to as Monica, who lacks most basic musical abilities, including melodic discrimination and recognition, despite normal audiometry and above-average intellectual, memory, and language skills. The results of psychophysical tests show that Monica has severe difficulties with detecting pitch changes. The data suggest that music-processing difficulties may result from problems in fine-grained discrimination of pitch, much in the same way as many language-processing difficulties arise from deficiencies in auditory temporal resolution.     

Inbreeding as a cause for deafness: Dadhkai study

BACKGROUND:

We report on the higher prevalence of deaf-mutes from a village in Jammu and Kashmir State of India.

MATERIALS AND METHODS:

A cross-sectional study among 79 deaf mutes using pedigree analysis, audiometry, imaging and molecular analysis.

RESULTS:

A high rate of hereditary deafness with 79 individuals diagnosed to be suffering from non-syndrome deafness in a total population of 2452 individuals residing in the village.

INTERPRETATION:

Flourishing of intermarriages led to a population with high prevalence of deafness     

The (r)evolution of cancer genetics

The identification of an increasing number of cancer genes is opening up unexpected scenarios in cancer genetics. When analyzed for their systemic properties, these genes show a general fragility towards perturbation. A recent paper published in BMC Biology shows how the founder domains of known cancer genes emerged at two macroevolutionary transitions - the advent of the first cell and the transition to metazoan multicellularity.     

The population genetics of a solitary oligolectic sweat bee, Lasioglossum (Sphecodogastra) oenotherae (Hymenoptera: Halictidae)

Strong evidence exists for global declines in pollinator populations. Data on the population genetics of solitary bees, especially diet specialists, are generally lacking. We studied the population genetics of the oligolectic bee Lasioglossum oenotherae, a specialist on the pollen of evening primrose (Onagraceae), by genotyping 455 females from 15 populations across the bee's North American range at six hyper-variable microsatellite loci. We found significant levels of genetic differentiation between populations, even at small geographic scales, as well as significant patterns of isolation by distance. However, using multilocus genotype assignment tests, we detected 11 first-generation migrants indicating that L. oenotherae's sub-populations are experiencing ongoing gene flow. Southern populations of L. oenotherae were significantly more likely to deviate from Hardy-Weinberg equilibrium and from genotypic equilibrium, suggesting regional differences in gene flow and/or drift and inbreeding. Short-term N(e) estimated using temporal changes in allele frequencies in several populations ranged from approximately 223 to 960. We discuss our findings in terms of the conservation genetics of specialist pollinators, a group of considerable ecological importance.     

Hereditary deafness in Kirov oblast: a genetic epidemiological study

The results of a genetic epidemiological study of hereditary deafness (HD) in ten raions (districts) of Kirov oblast (administrative region), Russia, are presented. A total of 122 075 people have been examined. Segregation analysis of all families with diagnosed HD has demonstrated a good fit to either the autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. The total prevalence rates of AD and AR HDs, as well as the specific prevalence rates of nonsyndromic and syndromic forms of HD, have been calculated for the population often raions. The HD prevalence rate in Kirov oblast has been found to be 1 : 1043 people (1 : 1453 and 1 : 3699 for the nonsyndromic and syndromic forms, respectively). This value has been found to vary in different raions, which is explained by differences in the genetic subdivision levels of the populations studied; the correlation coefficient between the HD load and random inbreeding (F(ST)) in district populations is r = 0.81 +/- 0.22. The diversity of syndromic hearing disorders is described.