The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

HIV-1 subtype B predominates in the Republic of Korea. Phylogenetic analyses of sequences for complete nef genes and env gene fragments encoding the V3 loop have identified a major monophyletic Korean subclade that is distinct from Western subtype B sequences in the Los Alamos HIV Sequence Database. This was investigated further by sequence analysis of complete env genes recovered from the DNA of peripheral blood mononuclear cells for matched groups of Koreans, four patients per group, previously assigned as being infected with either Korean or Western strains. The phylogenetic classifications were confirmed and analysis of the translation products identified 32 amino acid signature pattern differences, dispersed throughout gp160, which differentiate the two subclades. Twenty-three of these positions map to epitopes recognized by HLA-I-restricted cytotoxic T-lymphocytes (CTL) as catalogued in the Los Alamos HIV Immunology Database. The remaining nine map at or close to sites predicted to be targets for immunoproteasomes that are involved in producing peptides that bind to MHC Class I. These results suggest that a founder effect in the Korean population is based on the spread of CTL-escape/host-adapted HIV-1 strains.

SUMMARYWe characterized and established relationships between the expression ofmembrane 2H4 (CD45RA) and UCHL1 (CD45RO) by enriched lymphocyte fractions prepared by selective immunomagnetic depletion of monoclonal antibody-defined populations. Cell fractions analysed in this study could be divided into two broad groups according to the presence (CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8dim+ and CD3+CD4-CD8-) or absence (CD3-CD4-CD8dim+ and CD3-CD4-CD8-) of the CD3 antigen. Preliminary studies confirmed a reciprocal relationship for CD45RA and CD45RO expression by major lymphoid components and further showed that the level or intensity of membrane 2H4 staining (2H4+, 2H4int and 2H4-) could be directly related to UCHLI expression. As a reflection of their differential functions, the various CD3+ populations examined showed much greater heterogeneity in 2H4 and UCHL1 expression. CD3+CD4+CD8-cells generally showed significant proportions of 2H4+, 2H4in' and 2H4-components, whereas the CD3+CD4-CD8+ population was characterized by a predominance of 2H4+ cells. The results of this current investigation further suggested a higher proportion of dual-positive (2H4+UCHL1 +) cells and a much greater degree of inter-individual variation than previously suspected. In contrast to CfJ3+ lymphocytes, natural killer (NK) associated CD3-CD4-CD8dim+ and CD3-CD4-CD8-populations were mostly 2H4+ with only minor 2H4'nt components and very low expression of UCHL1. An additional observation of note was that the proportions of 2H4+ and 2H4-cells comprising the CD4+CD8-fraction in any given individual was highly correlated (P=0-002) with the distributions of 2H4+ and 2H4-components within the CD4-CD8+ fraction. This suggests the possible existence of a common control mechanism for the acquisition of immunological memory by distinct lymphocyte populations and further indicates that individual variations in the distribution of 2H4/UCHL1 lymphocyte subpopulations may be a direct consequence of 'immunological experience' rather than age alone.

Dendritic cells (DC) are targets for HIV-1 infection and may harbor distinct populations of virus variants. To test this hypothesis full length env genes have been amplified and sequenced from DC and T cells purified from the blood of five symptomatic HIV-1-infected patients. For three of the patients, showing slow and slow/standard disease progression, distinct subsets of HIV variants infected DC and T cells, and the diversity of the DC-derived env genes was less than that observed in T cells. Amino acid substitutions differentiating DC and T cell variants were dispersed throughout the length of the glycoproteins and were patient/HIV-1 strain specific. However, the V1 and V2 domains of T cell-derived clones were generally shorter than those from DC. These findings suggest that there may be distinct populations of HIV-1 variants infecting blood DC and T cells in patients showing slow and slow/standard disease progression.