A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

The daily periodicity of growth increment formation in sagittal otoliths of jack mackerel Trachurus japonicus was validated by marking otoliths with alizarin complexone (ALC). Analysis of otoliths of known-age juveniles confirmed that the first increment formed on day 3 after hatching, and was associated with first feeding. A total of 198 specimens, ranging from 2Á6 to 49Á2 mm in body length (notochord length or standard length) and from 7 to 78 days in age, were collected in the East China Sea and Tosa Bay, and used to examine the association between otolith morphological development and ontogenetic development. The relationship between body length (L) and otolith radius (R) was significantly described by the linear function L ¼ 2Á65 þ 0Á0425R (n ¼ 198, r 2 ¼ 0Á99, P < 0Á001), indicating that somatic growth history can be reconstructed from otolith growth patterns. The otolith was primarily spherical in the preflexion larval stage, and became elongated with notochord flexion. The first secondary primordium formed at c. 25 days, during the middle postflexion stage, and was associated with metamorphosis. By c. 42 days the sagittal otolith was adult-like in morphology, with the primary growth zone enclosed by the marginal growth zone, except in the anterior rostrum area. Thus age, growth and developmental stages were recorded in sagittal otoliths during the larval and early juvenile stages of jack mackerel. # 2005 The Fisheries Society of the British Isles

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We used mitochondrial DNA sequences to determine the phylogenetic placement of southern smelts (Retropinnidae), a group of diadromous fishes endemic to New Zealand and Australia. Our genetic data strongly support a sister group relationship between retropinnids and northern hemisphere smelts (Osmeridae), a relationship that seems consistent with the similar appearance and life history strategies of these two groups. Our analysis indicates that Retropinnidae and Osmeridae together represent the sister group to the southern hemisphere galaxiid fishes (Galaxiidae). However, this finding conflicts with several recent osteological analyses, which supported a sister relationship for Retropinnidae and Galaxiidae, giving a monophyletic southern hemisphere assemblage (Galaxioidea). We review cases of incongruence and discuss factors that might explain significant disagreement between molecular and morphological data matrices. We suggest that repeated evolutionary simplification may have undermined the accuracy of morphological hypotheses of osmeroid relationships. Although equally weighted parsimony analysis of morphological data rejects the molecular hypothesis (Osmeridae + Retropinnidae), implementation of a range of weighting schemes suggests that incongruence is nonsignificant under asymmetric character transformation models. We propose that a simple "equal transformation cost" parsimony analysis may be biologically unrealistic, especially when reductive homoplasy is widespread; as is increasingly being accepted, complex character states are more readily lost than gained. Therefore, we recommend that morphological systematists routinely implement a range of character transformation models to assess the sensitivity of their phylogenetic reconstructions. We discuss the antitropical biogeography of osmeroid fishes in the context of vicariance and transequatorial dispersal.

Environmental variability and growth-rate histories from hatching to capture were investigated for larval Japanese sardine (Sardinops melanostictus) and Japanese anchovy (Engraulis japonicus). Larvae collected around the front of the Kuroshio Current were examined using otolith microstructure analysis, and their movement was estimated from numerical particletracking experiments. Sardine larvae collected inshore of the Kuroshio front originated from a coastal area near the sampling site, while those collected in the offshore area originated from an area 500-800 km west-southwest of the sampling site. Anchovy larvae collected both inshore and offshore had been transported from widely distributed spawning areas located west of the sampling area. At the age of 13-14 days for sardine and 19-20 days for anchovy, the offshore group exhibited significantly higher mean growth rates than did the inshore group. Although the offshore area was generally warmer than the inshore area, temporal variations in growth rate are not attributable solely to fluctuations in environmental temperature. While previous studies have examined the relationship between larval growth rates and environment based solely on data at capture, the methods used in the present study, combining otolith analysis and numerical particle-tracking experiments, utilize data up until hatching. Although the relationship between growth rate and environment was not fully confirmed, this approach will greatly advance our understanding of fish population dynamics.