Unrelated Adults Research Articles

Genome-Wide Analysis of Copy Number Variation in Type 1 Diabetes

Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D.

Parentage testing of racing camels (Camelus dromedarius) using microsatellite DNA typing

The camel racing industry would have added value in being able to assign parentage with high certainty. This study was aimed at assessing and applying microsatellite multiplexes to construct a parentage testing system for camels. An efficient system of 17 loci from 700 camel samples was used to construct a database of unrelated adults. Based on this, we estimated measures of polymorphism among the markers. In three multiplex reactions, we detected a total of 224 alleles, with 5–23 alleles/locus (mean = 13.18 ± 6.95 SD) and an average heterozygosity (HE) of 0.54 (range 0.032–0.905). The total parentage exclusion probability was 0.99999 for excluding a candidate parent from parentage of an arbitrary offspring, given only the genotype of the offspring, and 0.9999 for excluding a candidate parent from parentage of an arbitrary offspring, given the genotype of the offspring and the other parent. We used 15 juveniles for parentage testing, as well as 17 sires (bull camels) and 21 dams (cows). In the case of parentage assignment, the microsatellite panel assigned all 15 offspring parentage with high confidence. Overall, these findings offer a set of microsatellite markers that are easy, simple and highly informative for parentage testing in camels.

Evaluation of Compressive Strength Index of the Femoral Neck in Caucasians and Chinese

Compressive strength index (CSI) of the femoral neck is a parameter that integrates the information of bone mineral density (BMD), femoral neck width (FNW), and body weight. CSI is considered to have the potential to improve the performance of assessment for hip fracture risk. However, studies on CSI have been rare. In particular, few studies have evaluated the performance of CSI, in comparison with BMD, FNW, and bending geometry, for assessment of hip fracture risk. We studied two large populations, including 1683 unrelated U.S. Caucasians and 2758 unrelated Chinese adults. For all the study subjects, CSI, femoral neck BMD (FN_BMD), FNW, and bending geometry (section modulus [Z]) of the samples were obtained from dual-energy X-ray absorptiometry scans. We investigated the age-related trends of these bone phenotypes and potential sex and ethnic differences. We further evaluated the performance of these four phenotypes for assessment of hip fracture risk by logistic regression models. Chinese had significantly lower FN_BMD, FNW, and Z, but higher CSI than sex-matched Caucasians. Logistic regression analysis showed that higher CSI was significantly associated with lower risk of hip fracture, and the significance remained after adjusting for covariates of age, sex, and height. Each standard deviation (SD) increment in CSI was associated with odds ratios of 0.765 (95% confidence interval, 0.634, 0.992) and 0.724 (95% confidence interval, 0.569, 0.921) for hip fracture risk in Caucasians and Chinese, respectively. The higher CSI in Chinese may partially help explain the lower incidence of hip fractures in this population compared to Caucasians. Further studies in larger cohorts and/or longitudinal observations are necessary to confirm our findings.

Measuring Financial Capability and its Determinants Using Survey Data

Financial capability, or people’s ability to manage and take control of their finances, is receiving increasing interest among policy makers as more people find themselves in difficult financial situations during the current economic downturn. We tackle the problem of how to measure financial capability—with a specific focus on making ends meet and money management—using data from a general household survey (the British Household Panel Survey), and then identify its key determinants using panel data models. This is important if appropriate policies and programmes are to be targeted at those most in need. We find the lowest financial capability among young unemployed single adults living in households with other unrelated non-working adults. In contrast, older men and women in full-time work with an employed spouse have the most financial capability.

Behavioral and genetic aspects of the raccoon mating system

Spatial dynamics and frequency of interaction between mating individuals are difficult to observe in the wild, and linking behavioral and genetic mating systems is particularly challenging for nocturnal or otherwise cryptic mammals. We monitored 29 (11 male and 18 female) adult raccoons in northeastern Illinois to gain a better understanding of how individuals interacted with one another during the mating season (December–March) of 2005. Adults were monitored with proximity-detecting radiocollars to determine the amount of spatial overlap and rate of contact among members of the local population, including those parent pairs that had mated successfully. We identified successful matings by conducting parentage analyses on 43 juveniles using 15 highly variable microsatellite loci. We were unable to identify parents for 25 of 43 juveniles, which greatly reduced our ability to assess the raccoon mating system. However, we present novel data on contact rates and den-sharing incidents between known parental pairs. We found that 3 of 4 parent pairs shared .35% of their daytime resting areas and .26% of their core resting areas. Contact rates of parent pairs varied, ranging from 0.1 to 0.9 contacts/day. Parent pairs were not observed to share dens during the mating season. However, among the remainder of the adult population, we found a sharp increase in instances of den sharing between unrelated adults that coincided with the peak of the mating season. Finally, male coalitions were not successful at sequestering breeding access to reproductive females; only 38.8% of juveniles were sired by males known to live in groups. DOI: 10.1644/09-MAMM-A-067.1.

Individual recognition and potential recognition errors in parent–offspring communication

The recognition of food-provisioning parents is crucial for fledglings of many bird species. Vocalizations are the most commonly used cues in avian parent–offspring communication, and it has been shown in several species that fledglings respond specifically to their parents' contact calls. However, fledglings occasionally also react to unrelated adults. Such responses may reflect recognition errors or alternatively a strategy of fledglings to obtain food or other direct benefits from unrelated adult birds. In a playback experiment, we tested whether zebra finch Taeniopygia guttata fledglings perceive variation in adult call signatures to recognize their parents and whether the propensity to respond to unrelated individuals is related to the gender of adults and to signal properties of male and female calls. Male calls are learnt and show high intra-sexual variation, which may improve the accurate recognition of the father's individual signature. In contrast, calls of adult females are innate, show lower intra-sexual variation such that the mother's call is more likely to be confused with another female call. We demonstrate that fledglings are able to recognize their parents. In addition, fledglings reacted more strongly to unrelated females compared with unrelated males. Our findings suggest that responses to unrelated adults may reflect recognition errors and indicate the importance of variation in identity signals for individual recognition processes in parent–offspring communication.

Adoption of Strange Chicks by Herring Gulls, Larus argentatus L

Adoption of young by unrelated adults is expected to be rare in natural populations, yet a high incidence was observed in a population of Herring Gulls on the Isle of May, Scotland. The means whereby rejection was avoided, and the resulting costs and benefits to adopting parents and adopted chicks, are described.

Cystic fibrosis with sarcoidosis—genetics vs immunology: a paradigm shift?

Introduction The authors describe coexistence of sarcoid and cystic fibrosis (CF), previously reported in only four childhood cases. Sarcoidosis has a UK annual incidence of 2–4 per 100 000 while CF is seen in 1/2000 live births. Rarity of both conditions makes coexistence by chance unlikely. Methods A 12-year-old girl, with pseudomonas positive CF (diagnosed age 7 months with positive sweat test and delta F508/1507 genotype), presented with a 2 year history of intermittent skin rash, joint pains, fever and conjunctivitis. Examination revealed petechial rash, hepatosplenomegaly and small joint arthritis. Results Investigations showed acute renal impairment (creatinine 200 μmol/l, eGFR 31, albumin/creatinine ratio 22.5 mg/mmol), elevated angiotensin converting enzyme levels (120 μ/l), hypercalcaemia (corrected- 4.57 mmol/l) and positive cANCA (non-PR3/MPO). Renal biopsy demonstrated granulomatous tubulo-interstitial nephritis. Conjunctival biopsy showed non-necrotising epitheloid granuloma. Skin biopsy revealed vasculitis and angiography demonstrated small vessel renal vasculitis. Chest x-ray was consistent with CF (normal CT chest, stable lung function). Treatment was given for sarcoid vasculitis using intravenous methylprednisolone, oral prednisolone and azathioprine. Persistent symptoms 7 months later led to substitution of azathioprine with mycophenolate mofetil and regular IVIG. Disease is currently well controlled. Frequent pseudomonas chest infections are problematic. Conclusion Increased incidence of CFTR mutations has been observed in twenty-six unrelated adults with sarcoidosis. Similarly, familial clustering with recurrence risk 1:100 among first-degree relatives and presence of HLA B8 and DR3 types has raised questions about common genetic aetiology. However, genotype analysis of families with two or more siblings with sarcoidosis failed to find evidence to support CFTR gene mutations. Sarcoid granulomas resemble those associated with mycobacteria, fungi or hypersensitivity. Aetiology remains obscure, but evidence favours chronic immunological response to unidentified environmental factors with possible genetic susceptibility. Both sarcoidosis and CF show defective T cell mediated immune functions and enhanced B cell activation. Children with CF develop frequent chest infections and progressive lung damage. Chronic immune stimulation with persistent antigenaemia and hyperimmunoglobulinaemia could generate large immune complexes resistant to phagocytosis, stimulating granuloma formation. CF may predispose to sarcoidosis through foreign material in the lung or by an altered immunological reaction.

Predictors of Self-Reported Likelihood of Working with Older Adults

This study examined the self-reported likelihood of working with older adults in a future career among 237 college undergraduates at a midsized Midwestern university. Although aging anxiety was not significantly related to likelihood of working with older adults, those students who had a greater level of death anxiety were less likely than other students to report a future likelihood of working with older adults. In addition, quality relationships with unrelated older adults were positively correlated with likelihood of working with older adults. Recommendations for future research and ideas for attracting college students to gerontology as a career are discussed.

Low expression of human β-defensin 1 in duodenum of celiac patients is partially restored by a gluten-free diet

Human beta-defensins (hBDs) are small cationic, widely expressed proteins involved in innate immunity that exert strong bactericidal activity toward various pathogens. However, the role of hBDs in various diseases to which bacterial infection add severity, as it is in celiac disease (CD), is not yet clear. We analyzed the expression of the hBD1, hBD2, hBD3 and hBD4 genes in patients with CD during the active phase and after remission following a gluten-free diet to determine their role in development and relapse of CD. We studied 21 unrelated adults with CD (confirmed by anti-thyroglobulin antibodies and intestinal biopsy); 14 were evaluated at diagnosis, before diet modification, and seven after 2 years of a gluten-free diet. Thirty-six unrelated adults served as controls. We analyzed the mRNA expression of hBD1, 2, 3 and 4 on biopsy samples of duodenum obtained from all patients during endoscopy for diagnostic purposes. We used real-time polymerase chain reaction with TaqMan probes and obtained gene expression data using the delta-Ct method. hBD1 mRNA was significantly lower in patients with active CD compared with patients on diet modification, whereas the mRNA levels of the other three defensins did not differ significantly between the two subgroups. Interestingly, the gluten-free diet restored only partially hBD1 expression as compared to a normal group of celiac-free subjects. Our data reinforce the evidence that hBD1 expression is greatly reduced in the duodenum of patients with active CD. It also strengthens the concept that reduced activity of immune peptides may predispose individuals to bacterial proliferation that contributes to the pathogenesis of CD.

Family and Household Formations and Suicide in the United States

Family support systems have been theoretically linked to suicide risk. But no research to date has investigated the effects of detailed living arrangements on individual risk of suicide. Using data on 825,462 adults from the National Health Interview Survey Linked Mortality File reveals that living in families with stronger sources of social support and integration decreases risk of suicide. These effects persist despite controls for important individual level characteristics. Risk of suicide decreases for persons in married as well as unmarried families when children are present and risk increases for persons living with unrelated adults. These results reveal the structural importance of family formation on the social integrative forces that contribute to an individual's risk of suicide.

Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population

Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG. Genomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced. Mutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients. PCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.

Assessing the impact of global versus local ancestry in association studies.

To account for population stratification in association studies, principal-components analysis is often performed on single-nucleotide polymorphisms (SNPs) across the genome. Here, we use Framingham Heart Study (FHS) Genetic Analysis Workshop 16 data to compare the performance of local ancestry adjustment for population stratification based on principal components (PCs) estimated from SNPs in a local chromosomal region with global ancestry adjustment based on PCs estimated from genome-wide SNPs. Standardized height residuals from unrelated adults from the FHS Offspring Cohort were averaged from longitudinal data. PCs of SNP genotype data were calculated to represent individual's ancestry either 1) globally using all SNPs across the genome or 2) locally using SNPs in adjacent 20-Mbp regions within each chromosome. We assessed the extent to which there were differences in association studies of height depending on whether PCs for global, local, or both global and local ancestry were included as covariates. The correlations between local and global PCs were low (r < 0.12), suggesting variability between local and global ancestry estimates. Genome-wide association tests without any ancestry adjustment demonstrated an inflated type I error rate that decreased with adjustment for local ancestry, global ancestry, or both. A known spurious association was replicated for SNPs within the lactase gene, and this false-positive association was abolished by adjustment with local or global ancestry PCs. Population stratification is a potential source of bias in this seemingly homogenous FHS population. However, local and global PCs derived from SNPs appear to provide adequate information about ancestry.

Mass Lead Poisoning in Dakar: Battery Recycling Exacts a Heavy Toll

In a neighborhood of Dakar, Senegal, 18 children died from an aggressive central nervous system disease between November 2007 and March 2008. Experts from the World Health Organization and local health authorities were called in to investigate the deaths, but cultural prohibitions preempted autopsies of the children. So the researchers examined 32 of the children’s siblings and 23 of the siblings’ mothers along with 18 unrelated local children and 8 unrelated adults. They concluded that the cause of death likely was encephalopathy resulting from severe lead poisoning [EHP 117:1535–1540; Haefliger et al.]. The source of the lead, in turn, was determined to be contamination resulting from the reclamation of used lead‐acid batteries, a lucrative business in developing countries that often is performed in the open with few pollution controls. Since 1995, local people had broken apart batteries from vehicles and appliances and sorted the components in an open sandy area of the neighbhorhood. They sifted through the sand for scraps of valuable lead to sell, even carrying sacks of contaminated sand into their homes. People were probably exposed by inhaling and ingesting lead dust, with children particularly exposed through hand‐to‐mouth activity and eating the contaminated soil. The developing nervous system of children is particularly vulnerable to the toxic effects of lead. Blood lead concentrations as low as 10 μg/dL are known to impair neurologic development, resulting in permanent intellectual impairment. However, recent evidence suggests there may be no safe threshold of exposure. Among the 50 children tested, blood lead levels ranged from 39.8 to 613.9 μg/dL. Seventeen of the 50 children showed neuropsychiatric symptoms including convulsions, irritability, and aggression, and 21 showed gastrointestinal symptoms such as anorexia and vomiting. Adult blood lead levels ranged from 32.5 to 98.9 μg/dL, and their most commonly reported symptom was gastrointestinal upset. Recycling activity reportedly ended by March 2008 following a public awareness campaign, and the neighborhood soil was partially remediated. Nevertheless, lead concentrations measured in the sandy work area after this time still reached 209,000 mg/kg, and levels inside homes reached 14,000 mg/kg. The U. S. Department of Housing and Urban Development sets 400 mg/kg as for the standard for lead in bare soil in children’s play areas (there is no comparable standard in Senegal). The lead poisoning in this study was severe enough to catch the attention of health experts, but the global incidence of lead poisoning from battery recycling is unknown. The authors believe many cases go unaddressed in developing countries because local authorities lack resources to recognize, diagnose, and manage lead toxicity. However, they write, lead poisoning can be prevented through measures such as public education and the implementation and enforcement of lead recycling guidelines.

Genome-Wide Association Study of Exercise Behavior in Dutch and American Adults

The objective of this study was to identify genetic variants that are associated with adult leisure time exercise behavior using genome-wide association (GWA) in two independent samples. Exercise behavior was measured in 1644 unrelated Dutch and 978 unrelated American adults of European ancestry with detailed questions about type, frequency, and duration of exercise. Individuals were classified into regular exercisers or nonexercisers using a threshold of 4 MET·h (metabolic equivalents-hours per week). GWA analyses of ∼1.6 million observed and imputed Single Nucleotide Polymorphism (SNP) were conducted in both samples independently using logistic regression in SNPTEST, including sex, age, and body mass index as covariates. A meta-analysis of the results was performed using the weighted inverse variance method in METAL. Thirty-seven novel SNPs in the PAPSS2 gene and in two intergenic regions on chromosomes 2q33.1 and 18p11.32 were associated with exercise participation (pooled P values <1.0 × 10(-5)). Previously reported associations (ACE, CASR, CYP19A1, DRD2, LEPR, and MC4R genes) or linkage findings (2p22.3, 4q28, 4q31.21 7p13, 9q31, 11p15, 13q22, 15q13, 18q12.2, 18q21.1, 19p13.3, and 20q12) were not replicated, although suggestive evidence was found for association to rs12405556 in the LEPR gene (pooled P value 9.7 × 10(-4); American sample, P value 9.8 × 10(-5)) and for association to rs8036270 in the GABRG3 gene (pooled P value 4.6 × 10(-5)) in the linkage region 15q12-13. The heritability of leisure time exercise behavior is likely to be accounted for by many genetic variants with small effect size. These can be detected by GWA as was shown here for the PAPSS2 gene, but larger samples with genome-wide genotypes and high-quality exercise data are needed for further progress.

The Upper Silesia (Poland) population and forensic usefulness of 11 autosomal STR loci

Allele frequencies, forensic parameters for the 11 STR loci in GenePrint STR Systems—Silver Stain Detection (Promega): CSF1PO, TPOX, TH01, D16S539, D7S820, D13S317, F13A01, FESFPS, VWA, F13B, LPL were determined in a sample of 529–1436 unrelated, dead and alive adults from the Upper Silesia region (Poland). Furthermore, gender identification was carried out. The values of heterozygosity (Ht), polymorphic information content (PIC), power of discrimination (PD), matching probability (PM), mean exclusion chance (MEC) and mean exclusion probability (MEP) were calculated using Dudek's computer programme (FatRec, High Technical School of Częstochowa, Poland). A possible divergence from HWE was determined by χ 2 and exact tests using Miller's computer programme (TFPGA, Northern Arizona University, Flagstaff, USA). Comparison of allele frequencies between the Upper Silesia population and other Polish populations was performed with Carmody's test.

The Upper Silesia (Poland) population and forensic usefulness of 15 autosomal STR loci

Allele frequencies, forensic parameters for the 15 STR loci in the AmpFlSTR ® Identifiler Kit (Applied Biosystems), D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D19S433, VWA, TPOX, D18S51, D5S818 and FGA were determined in a sample of 150 unrelated dead and alive adults from the Upper Silesia region (Poland). The values of heterozygosity (Ht), polymorphic information content (PIC), power of discrimination (PD), matching probability (PM), mean exclusion chance (MEC) and mean exclusion probability (MEP) were calculated. Possible divergence from HWE was determined. Comparison of allele frequencies for examined STR loci between the Upper Silesia population and other Polish populations was carried out.

Sociality improves larval growth in the stag beetle Figulus binodulus (Coleoptera: Lucanidae)

The benefits for offspring of attendant adult were investigated in the stag beetle Figulus binodulus. The initial growth rate of third-instar larva was significantly higher when the larvae were in a nest with adults compared to those in a nest without adults. The difference in growth rate is reflected in adult body size. Although the presence of adult beetle generally benefited the offspring, the adults did eat some of the larvae. Filial cannibalism was the primary cause of juvenile death in nests with adults. Mortality was lower in nests with adults related to the juveniles compared to nests with unrelated adults, suggesting that infanticide of nest mates may be inhibited. These results suggest that F. binodulus has a level of sociality and nest mate recognition that is very rare in stag beetles. Social behaviour may be more advantageous for small stag beetles than fighting.

Clinical spectrum of ataxia-telangiectasia in adulthood

To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity. Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations. Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.

Isolation and characterization of polymorphic microsatellite loci for the northern flicker (Colaptes auratus; Aves)

To investigate the mating system of northern flickers (Colaptes auratus), we developed primers for 14 microsatellite loci and screened them in 68 unrelated adults and their offspring. All markers were highly polymorphic with 9 to+36 alleles per locus. One marker was Z-chromosome linked; one marker exceeded the size standard range and could not be analysed further. We checked the other 12 markers for Mendelian inheritance in 36 broods for which the social parents were known. Seven markers showed evidence for the presence of null alleles, and three of those showed significant deviation from Hardy-Weinberg equilibrium. Markers were generally unlinked.