Chromosome 9 of Ellobius lutescens is the X chromosome

Ellobius lutescens carries an apparently identical karyotype (2n = 17) in both sexes. On the basis of indirect evidence the unpaired chromosome 9 has been considered to represent the X chromosome of this species. We have obtained data to substantiate this view by four different techniques. After fusion of HPRT- RAG cells with E. lutescens fibroblasts we demonstrated that the enzymes HPRT and G6PD are localized on the presumptive X chromosome. By analysis of pachytene figures after silver staining we showed by electron microscopy that the single chromosome exhibits the typical features of an X chromosome in male meiosis. Hybridization of (GATA)4 and (GACA)4 oligonucleotide probes to E. lutescens DNA revealed several distinct bands in the high molecular weight range some of which appeared to be specific for the individual but not for the sex of the animal. Hybridization in situ of the (GATA)4 probe on metaphase spreads of E. lutescens did not highlight any particular chromosome segment but showed a significant deficit of these sequences in chromosome 9. These observations are discussed with respect to their bearing on X chromosome determination. Finally it is concluded that E. lutescens should be an ideal tool for testing candidate genes assumed to be involved in primary sex determination

AZFc region of the Y chromosome shows singular structural organization

Owing to clonal inheritance, haploid status and lack of recombination, structural polymorphism in the human Y chromosome is more prevalent than that in the remaining parts of the genome. We studied structural organization of the AZFc region, assessed microdeletions therein and studied copy number variation (CNV) of several candidate genes in 750 Indian males. FISH mapping of 13 Y-specific BAC/cosmid clones uncovered a hitherto unreported AZFc configuration showing inter-DAZ gene sequence onto the Yp instead of Yq region. Such inter-DAZ gene arrangements were also detected in five German males (European Y). In 40–50% males, partial u3 and one of the green amplicons, g1, g2 or g3 was present on the Yp in addition to Yq, suggesting an alteration in the IR3 region. Among other AZFc candidates, complete TTY3 and partial CDY1 BAC sequences were detected on the proximal 5p and distal 15q regions, respectively, in both the sexes. However, primers deduced from these clones showed male specific amplification of TTY3 and CDY1 exons suggesting (re)organization of their flanking sequences between Y and autosomes. Importantly, ∼5% males showed CNV of various Y-linked genes, and ∼3%, random microdeletions across the AZF region. Present study demonstrates hitherto unreported singular structural organization with respect to DAZ, TTY3 and CDY1 genes highlighting organizational complexities of the human Y chromosome in the global context

Mutation analysis of the neurofilament M gene in Parkinson's disease.

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. These substitutions affect residues of the NF-M protein that are highly conserved among different species. None of our patients carried the Gly336Ser substitution, which has been described in familial PD. Our results argue against a major role of NF-M in PD. However, rare variants of the NF-M gene may act as susceptibility factors for PD and functional analyses of the identified variations are warranted to decipher possible mechanisms in neurodegeneration