Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

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Using a subtractive cDNA cloning strategy, we isolated previously five novel genes that were expressed abundantly by the murine dendritic cell (DC) line XS52, but not by the J774 macrophage line. One of these genes encoded a unique, DC-associated C-type lectin, termed "dectin-1." Here we report the characterization of a second novel gene that was also expressed in a DC-specific manner. Clone 1B12 encoded a type II membrane-integrated polypeptide of 209 amino acids containing a single carbohydrate recognition domain motif in the COOH terminus. The expression pattern of this molecule, termed "dectin-2," was almost indistinguishable from that for dectin-1; that is, both were expressed abundantly at mRNA and protein levels by the XS52 DC line, but not by non-DC lines, and both were detected in spleen and thymus, as well as in skin resident DC (i.e. Langerhans cells). Interestingly, reverse transcriptasepolymerase chain reaction and immunoblotting revealed multiple bands of dectin-2 transcripts and proteins suggesting molecular heterogeneity. In fact, we isolated additional cDNA clones encoding two distinct, truncated dectin-2 isoforms. Genomic analyses indicated that a full-length dectin-2 (␣ isoform) is encoded by 6 exons, whereas truncated isoforms (␤ and ␥) are produced by alternative splicing. We propose that dectin-2 and its isoforms, together with dectin-1, represent a unique subfamily of DC-associated C-type lectins. Dendritic cells (DC)1 are far more potent than other antigenpresenting cells (e.g. macrophages and B cells) in their capacity to activate immunologically naive T cells, and DC are, indeed, responsible for initiating T cell-mediated immune responses to a variety of antigens (1, 2). Members of the DC family are distributed to virtually all the organs (except the brain), where they serve as tissue resident antigen-presenting cells, playing critical roles in presenting environmental, microbial, and tumor-associated antigens to the immune system.Several years ago, we developed stable DC lines from the mouse epidermis (3). These lines, termed as the XS series, maintain many important features of skin resident DC, i.e. Langerhans cells, and they have provided a useful tool for the application of modern technologies for studying DC biology (3-13). Most recently, we employed the subtractive cDNA cloning strategy to identify genes that were expressed preferentially by DC. 2 Briefly, we constructed a DC-specific cDNA library by subtracting cDNAs prepared from the XS52 DC line with excess amounts of mRNAs isolated from the J774 macrophage line. Following three rounds of screening of this library, we identified five novel genes that were expressed selectively by XS52 DC, but not by J774 macrophages. One of these genes encoded a type II membrane-associated polypeptide of 244 amino acids (aa) containing a single carbohydrate recognition domain (CRD) motif at the COOH-terminal end. This polypeptide was, therefore, designated as DC-associated C-type (Ca 2ϩ -dependent) lectin-1 or dectin-1. Dectin-1 mRNA was expre...

Within recent years, microsatellite have become one of the most powerful genetic markers in biology. For several mammalian species, microsatellite mutation rates have been estimated on the order of 10(-3)-10(-5). A recent study, however, demonstrated mutation rates in Drosophila melanogaster of at least one order of magnitude lower than those in mammals. To further test this result, we examined mutation rates of different microsatellite loci using a larger sample size. We screened 24 microsatellite loci in 119 D. melanogaster lines maintained for approximately 250 generations and detected 9 microsatellite mutations. The average mutation rate of 6.3 x 10(-6) is identical to the mutation rate from a previous study. Most interestingly, all nine mutations occurred at the same allele of one locus (DROYANETSB). This hypermutable allele has 28 dinucleotide repeats and is among the longest microsatellite reported in D. melanogaster. The allele-specific mutation rate of 3.0 x 10(-4) per generation is within the range of mammalian mutation rates. Future microsatellite analyses will have to account for the dramatic differences in allele-specific mutation rates.

Purpose Determine 1) if levels of the glycocalyx membrane mucins, MUC1 and MUC16, and the secreted goblet cell mucin MUC5AC are altered in conjunctival cells and tears of postmenopausal women presenting with a history of non-Sjögren's dry eye, and 2) if mucin levels correlate with dry eye clinical diagnostic data. Methods Eighty-four postmenopausal women with a history of non-Sjögren's dry eye and 30 normal subjects were recruited for this study. Impression cytology samples were collected for mucin mRNA and protein analysis. Tears were collected for mucin protein assay. qPCR, western blot, and ELISA assays were used to quantitate MUC1, MUC16 and MUC5AC levels. Results Postmenopausal women with a history of dry eye displayed significantly increased MUC1 mRNA expression and cellular protein compared to normal subjects (P<0.001 and P<0.0l, respectively). Similarly, cellular MUC16 protein levels were significantly higher (P<0.001). Mucin levels were found to be correlated with the clinical characterization of the subjects, including staining and symptoms. Although cellular MUC5AC protein levels were increased in symptomatic subjects, the increase did not reach statistical significance. Conclusion Elevation in MUC1 and MUC16 mRNA and/or protein levels in postmenopausal non-Sjögren's dry eye patients with a history of dry eye may be a compensatory response to irritation and inflammation associated with the disease. Understanding the pattern of mucin expression associated with dry eye pathology may clarify factors involved in the progression of the disease and enhance the development of targeted therapies.

Langerhans cells (LC)

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