Localisation of a gene implicated in a severe speech and language disorder

@article{Fisher1998LocalisationOA,
  title={Localisation of a gene implicated in a severe speech and language disorder},
  author={Simon E. Fisher and Faraneh Vargha-Khadem and Kate E. Watkins and Anthony P. Monaco and Marcus E Pembrey},
  journal={Nature Genetics},
  year={1998},
  volume={18},
  pages={168-170}
}
Between 2 and 5% of children who are otherwise unimpaired have significant difficulties in acquiring expressive and/or receptive language, despite adequate intelligence and opportunity1,2. While twin studies indicate a significant role for genetic factors in developmental disorders of speech and language1, the majority of families segregating such disorders show complex patterns of inheritance, and are thus not amenable for conventional linkage analysis2. A rare exception is the KE family, a… 

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References

SHOWING 1-10 OF 23 REFERENCES

Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder.

TLDR
Investigations of the same KE family indicate that the inherited disorder has a broad phenotype which transcends impaired generation of syntactical rules and includes a striking articulatory impairment as well as defects in intellectual, linguistic, and orofacial praxic functions generally.

GENETIC BASIS OF SPECIFIC LANGUAGE IMPAIRMENT: EVIDENCE FROM A TWIN STUDY

TLDR
There is good evidence that genetic factors play a role in the aetiology of speech and language impairment; twin data may help to arrive at a clearer conception of the phenotype as well as quantifying the extent of the genetic contribution.

An extended Family with a Dominantly Inherited Speech Disorder

A three‐generation family is described in which 16 members have a severe developmental verbal dyspraxia. Inheritance is autosomal dominant, with full penetrance. Intelligence and hearing are normal.

A comprehensive genetic map of the human genome based on 5,264 microsatellites

TLDR
The last version of the Généthon human linkage map is reported, which consists of 5,264 short tandem repeat polymorphisms with a mean heterozygosity of 70%.

A Gene Map of the Human Genome

TLDR
The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease.

A physical map of human chromosome 7: an integrated YAC contig map with average STS spacing of 79 kb.

TLDR
The physical map of human chromosome 7, a approximately 170-Mb segment of DNA that corresponds to an estimated 5% of the human genome, exceeds the goal of 100-kb average STS spacing and should provide an excellent framework for systematic sequencing of the chromosome.

Periventricular Leukomalacia: Ultrasonic and Neuropathological Correlations

TLDR
Ultrasound scans of a preterm neonate at seven weeks of age showed periventricular echo‐ free cavities, but these were no longer visible at 15 weeks, three weeks before the infant died, demonstrating that transient echo‐free cavities represent foci of cystic necrosis, which are subject to secondary collapse.

Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.

TLDR
Algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis are explored.

Chromosome–specific microsatellite sets for fluorescence–based, semi–automated genome mapping

To facilitate large–scale genetic mapping of the human genome, we have developed chromosome–specific sets of microsatellite marker loci suitable for use with a fluorescence–based automated DNA