Opportunistic feeding in Sceloporus horridus from Jalisco, Mexico

Based on a sample of 17 adult specimens of Sceloporus horridus taken near Autlan, Jalisco, Mexico in May 1974 just before and just after the first rainfall of the year, we present the first published data on the food habits of this lizard. Important prey item taxa were Homoptera, Coleoptera, Hymenoptera, Orthoptera, and Isoptera. The absence of Homoptera and Orthoptera, and the concomitant greater relative importance of Isoptera and Hymenoptera in the diet after the rain than before indicates opportunistic feeding by S. horridus. Our data suggest that reproduction in this lizard is probably initiated soon after the first rains in late spring.     

Condition models for wintering Northern Pintails in the Southern High Plains

Three condition models for wintering Northern Pintails ( Anas acuta ) were tested for their ability to predict fat mass, logarithm of fat mass, or a condition index (CI) incorporating fat mass. Equations generated to predict fat mass and the logarithm of fat mass accounted for more than 69% of the variation in these dependent variables. Log transformations of body mass, wing length, and total length explained at least 60% of the variation in CI. All models performed better on an independent data set. Mean prediction error was minimal (≤8% of measured variables) and negative for all models. Regression models apply to live and dead pintails and thus represent tools that have utility in a wide variety of studies on pintail condition.     

Seasonal trends and colonization patterns of macroinvertebrate assemblages in two streams with contrasting flow regimes

Patterns of colonization by macroinvertebrates were examined in two streams that differ in flow regime: a snowmelt system and a mesic groundwater system. Experiments were conducted during spring runoff, summer baseflow, and winter baseflow using artificial substrata. Colonization patterns reflected seasonal changes in benthic macroinvertebrate assemblages and life histories in each stream. The density and biomass of benthic organisms were approximately 3X greater in winter than in either spring or summer for both streams. Similarly, colonization was greater in winter than in spring or summer for both streams. In spring, colonization patterns were different between streams, with colonization being imperceptible in the snowmelt stream. Macroinvertebrate abundance fluctuated during the summer colonization experiment at both sites, resulting from a complex interplay among population emergence, recruitment, and/or movement. Assemblages in the snowmelt system primarily comprised mobile or ruderal taxa, such as Beatis tricaudatus and Chironomidae, whereas relatively sessile taxa, such as Glossoma nigrior , were predominant in the mesic groundwater system. Seasonal patterns of colonization differed among stream types primarily because of the profound interplay of flow regime and temperature on benthic community structure and organism life history.     

Bayesian inference of ancient human demography from individual genome sequences

Whole-genome sequences provide a rich source of information about human evolution. Here we describe an effort to estimate key evolutionary parameters based on the whole-genome sequences of six individuals from diverse human populations. We used a Bayesian, coalescent-based approach to obtain information about ancestral population sizes, divergence times and migration rates from inferred genealogies at many neutrally evolving loci across the genome. We introduce new methods for accommodating gene flow between populations and integrating over possible phasings of diploid genotypes. We also describe a custom pipeline for genotype inference to mitigate biases from heterogeneous sequencing technologies and coverage levels. Our analysis indicates that the San population of southern Africa diverged from other human populations approximately 108-157 thousand years ago, that Eurasians diverged from an ancestral African population 38-64 thousand years ago, and that the effective population size of the ancestors of all modern humans was ～9,000.     

The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.     

CEP152 is a genome maintenance protein disrupted in Seckel syndrome

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.     

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.     

Identification of low-frequency variants associated with gout and serum uric acid levels

We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.     

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.