Variant Map Research Articles

Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11p15 and 15q21-23.

The childhood neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative disorders characterised by progressive visual failure, neurodegeneration, epilepsy and the accumulation of an autofluorescent lipopigment in neurones and other cells. Three main subtypes have been identified according to age of onset, clinical features and ultrastructural morphology. These are infantile NCL (INCL; CLN1), classical late infantile NCL (LINCL; CLN2) and juvenile NCL (JNCL; CLN3). Several atypical forms of late infantile NCL (LINCL) have also been described including a Finnish variant LINCL (CLN5). The CLN2 gene has been excluded from the CLN1, CLN3 and CLN5 loci. A genome search was initiated using a homozygosity mapping strategy in five classical LINCL and two variant LINCL consanguineous families. A common region of homozygosity was identified on chromosome 11p15 in two of the classical families. Analysis of a further 33 classical LINCL families supported linkage in this region (Zmax = 3.07 at theta = 0.06 at D11S1338). A common region of homozygosity was also observed on chromosome 15q21-23 in the two variant LINCL families. Extension of the analysis to include a further seven families of identical ultrastructural phenotype established linkage to this region (Zmax = 6.00 at theta = 0.00 at D15S1020).

Capillary zone electrophoresis and mass spectrometry for the characterization of genetic variants of human hemoglobin

This paper describes a simple and rapid analytical method for the structural identification of abnormal human hemoglobins. Globin chains obtained by precipitation of erythrocyte hemolysate in cold acetone are directly analyzed by capillary zone electrophoresis in coated capillaries without any prior treatment. The speed and the high resolving power of capillary zone electrophoresis allow fast differentiation of hemoglobins with similar charges. Capillary zone electrophoretic tryptic mapping has also been performed for each globin, so that complete variant characterization can be achieved by direct comparison of the variant tryptic map with the corresponding normal one. Coupling electrophoretic data with analysis of enzymatic digests by mass spectrometry according to the “fast atom bombardment mapping” procedure makes it possible to quickly identify amino acid variations. This paper describes how the method can be applied to the characterization of common and uncommon variants and underlines the advantages and limitations of the procedure along with its potential uses in structural analysis of proteins.