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Volume 82 Issue 4  April 11th, 2008
(Next issue: May 9th, 2008)

Leber hereditary optic neuropathy (LHON) was the first disease recognized to be inherited via the cytoplasm. In 1931, Julia Bell noted that the disease was only inherited maternally and, in contrast to X-linked diseases, did not show up in later descendents of affected males (Hereditary optic atrophy [Leber's Disease] In: Treasury of Human Inheritance, vol 2 part iv Pearson, K. [ed.] Cambridge: Cambridge University Press, 325–423.) Imai and Moriwaki later proposed in 1936 that the disease was being inherited through the cytoplasm and not the nuclear chromosomes (Journal of Genetics 33: 163–167). More than 50 years later, in 1998, Wallace et al. identified a mitochondrial DNA (mtDNA) mutation in several LHON families (Science 242: 1427–1430). On the cover, the funduscopic picture of the left eye of an 18 year old with LHON. A maternal cousin had lost vision in a similar fashion two years prior and had tested positive for the mtDNA 11778 mutation. Special thanks to Nancy J. Newman, M.D., Emory University School of Medicine, for the image and assistance with the summary text.

Latest Articles

The American Journal of Human Genetics publishes papers online ahead of the print issue on a weekly basis. This week's posting includes papers on evidence for natural selection on receptors recognizing HLA, markers associated with IBD, GWAS for C-reactive protein levels, RBM28 mutations in an alopecia syndrome, analysis of mtDNA lineages in sub-Saharan Africa, UQCRQ mutations in a mitochondrial complex III disease, and a genome-wide analysis of the relationship between SNPs and gene expression. Click here to see all papers not yet in print.

Featured Articles

	Multilocus Meta -Analysis Meta-analyses can increase sample size and power to detect an association, but difficulties arise when the studies being combined genotype different markers. Verzilli et al. develop a method that incorporates LD from databases or other studies to incorporate data for all markers across all studies.
	Human Mitochondrial Substitution Rate In order to accurately date events with mtDNA, a trustworthy measurement of mtDNA substitution rates needs to be established. Endicott and Ho develop a Bayesian-model-based measurement to estimate substitution rates and evaluate calibration methods to determine time to most recent ancestor.
	SNP Arrays in Heterogeneous Tissue Samples Because of the importance of determining the genetic differences between normal tissue and cancer cells, methods have been developed to compare germline and somatic genotypes. Assié et al. introduce SOMATICs, which uses the normal cells within a tumor sample as an internal control.
	Small RNAs Mapping in ENCODE Regions The importance of noncoding RNAs has been recognized in work including studies of antisense RNAs and microRNAs. To learn more about RNAs in the genome, Borel et al. comprehensively analyze and characterize the small RNAs, 19–50 nucleotides in length, generated from within the 44 ENCODE regions.
	Identification of the SPG15 Gene A locus for SPG15, a complicated and autosomal recessive (AR) form of hereditary spastic paraplegia (HSP), was recently mapped to 14q22-q24 in two Irish families. Hanein et al. study eight SPG15 families to further refine the locus and determine that ZFYVE26 is disrupted in this form of AR-HSP.

Featured Review from Trends in Genetics

The use of alternative promoters adds to the complexity of the human genome. Recent evidence suggests that almost half of the protein-coding genes in humans contain alternative promoters and aberrant promoter use is often associated with disease. In this review, Ramana V. Davuluri and colleagues describe the consequences of alternative promoter usage in mammalian genomes.

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