The effects of varied densities on the growth and emigration of adult cutthroat trout and brook trout in fenced stream enclosures

We evaluated the effects of various density treatments on adult fish growth and emigration rates between Bonneville cutthroat trout Oncorhynchus clarki utah and brook trout Salvelinus fontinalis in stream enclosures in Beaver Creek, Idaho. We used 3 density treatments (low, ambient, and high fish densities) to evaluate density-related effects and to ensure a response. Intraspecific ambient-density tests using cutthroat trout only were also performed. Results indicated an absence of cage effects in the stream enclosures and no differences in fish growth between ambient-density stream-enclosure fish and free-range fish. Brook trout outgrew and moved less than cutthroat trout in the stream enclosures, especially as density increased. In all 3 density treatments, brook trout gained more weight than cutthroat trout, with brook trout gaining weight in each density treatment and cutthroat trout losing weight at the highest density. At high densities, cutthroat trout attempted to emigrate more frequently than brook trout in sympatry and allopatry. We observed a negative correlation between growth and emigration for interspecific cutthroat trout, indicating a possible competitive response due to the presence of brook trout. We observed similar responses for weight and emigration in trials of allopatric cutthroat trout, indicating strong intraspecific effects as density increased. While cutthroat trout showed a response to experimental manipulation with brook trout at different densities, there has been long-term coexistence between these species in Beaver Creek. This system presents a unique opportunity to study the mechanisms that lead cutthroat trout to coexist with rather than be replaced by nonnative brook trout.     

A radioimmunoassay of vasopressin. A note on pituitary vasopressin content in brattleboro rats

Zusammenfassung Die Empfindlichkeit und Zuverlässigkeit eines neu entwickelten Radioimmunotests für Vasopressin wurde durch Messungen des Vasopressinspiegels im Hypophysenhinterlappen von homozygoten und heterozygoten Ratten für angeborenen Diabetes insipidus geprüft und eine gute Korrelation zwischen dem biologisch und radioimmunologisch gemessenen Vasopressingehalt der Hypophyse nachgewiesen.     

Segregation at three loci explains familial and population risk in Hirschsprung disease

Hirschsprung disease (HSCR), the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance. Coding sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). We conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be necessary and sufficient to explain recurrence risk and population incidence. The gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in only 40% of linked families, suggesting the importance of noncoding variation. Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET. This study demonstrates by a complete genetic dissection why the inheritance pattern of S-HSCR is nonmendelian.     

A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer

We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.     

A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig

Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation.     

A role for MLH3 in hereditary nonpolyposis colorectal cancer

We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations, in 12 patients suspected of HNPCC. Three of the 12 also carried a mutation in MSH6.