Isolation and characterization of alphoid DNA sequences specific for the pericentric regions of chromosomes 4, 5, 9, and 19

We have cloned and characterized two distinct types of alphoid DNA elements. Probe pG-Xba 11/340 was obtained by random cloning of human satellite DNA and contains two basic units with overall 88% homology to the 171-bp consensus alphoid sequence. pG-Xba 11/340-like elements are represented about 2,000-4,000 times in the haploid genome and, by in situ hybridization, are found exclusively at the primary constrictions of chromosomes 4 and 9. Probe pG-A16 was cloned from a chromosome 19-specific cosmid library and represents a 2.25-kb higher-order DNA element which is present at roughly 75-150 copies per haploid genome and which hybridizes to the centromeres of chromosomes 5 and 19. Using the pG-A16 probe, further genetic and physical dissection of the central area of chromosome 19 can be envisaged.     

Family with neurofibromatosis type 2 and autosomal dominant hearing loss: identification of carriers of the mutated NF2 gene

A family is presented in which neurofibromatosis type 2 (NF2) and autosomal dominant hearing loss segregate in an apparently independent way. The presence of the latter condition caused anxiety in all family members at risk for NF2 in whom hearing loss became apparent. Previously, we identified a G A transition in the donor splice site of exon 5 of the NF2 gene in a family member with proven NF2. As expected, the mutation was present in two other family members who fulfilled the diagnostic criteria for NF2. Four out of five family members at risk for NF2 developed hearing loss. Two of these had the G A transition. The mutation was absent in the two other individuals with hearing loss and in the fifth family member without hearing loss or other clinical symptoms. In this family, the identification of the underlying NF2 gene mutation excluded NF2 as the cause of hearing loss in two potential carriers of the mutated gene. On the other hand, it enabled the identification of two carriers of the NF2 gene mutation who did not fulfill the diagnostic criteria for NF2. They will have to be monitored very carefully for the development of NF2-associated tumors. The consistent association within this family of a relatively mild clinical phenotype with the NF2 mutation, supports earlier suggestions that intrafamilial variability is small in NF2     

Evolutionary relationships among the male and female mitochondrial DNA lineages in the Mytilus edulis species complex

A novel form of mitochondrial DNA (mtDNA) inheritance has previously been documented for the blue mussel (Mytilus edulis). Female mussels inherit their mtDNA solely from their mother while males inherit mtDNA from both their mother and their father. In males, the paternal mtDNA is preferentially amplified so that the male gonad is highly enriched for the paternal mtDNA that is then transmitted from fathers to sons. We demonstrate that this mode of mtDNA inheritance also operates in the closely related species M. galloprovincialis and M. trossulus. The evolutionary relationship between the male and female mtDNA lineages is estimated by phylogenetic analysis of 455 nucleotides from the large subunit ribosomal RNA gene. We have found that the male and female lineages are highly divergent; the divergence of these lineages began prior to the speciation of the three species of blue mussels. Further, the separation between the male and female lineages is estimated to have occurred between 5.3 and 5.7 MYA.