Associations of PON1 and genetic ancestry with obesity in early childhood.

Obesity in children has become an epidemic in the U.S. and is particularly prominent in minority populations such as Mexican-Americans. In addition to physical activity and diet, genetics also plays a role in obesity etiology. A few studies in adults and adolescents suggest a link between obesity and paraoxonase 1 (PON1), a multifunctional enzyme that can metabolize organophosphate pesticides and also has antioxidant properties. We determined PON1192 genotype and arylesterase levels (ARYase, measure of PON1 enzyme quantity), to characterize the relationship between PON1 and obesity in young Mexican-American children (n = 373) living in an agricultural community in California. Since PON1 polymorphisms and obesity both vary between ethnic groups, we estimated proportional genetic ancestry using 106 ancestral informative markers (AIMs). Among children, PON1192 allele frequencies were 0.5 for both alleles, and the prevalence of obesity was high (15% and 33% at ages two and five, respectively). The average proportion of European, African, and Native American ancestry was 0.40, 0.09, and 0.51, yet there was wide inter-individual variation. We found a significantly higher odds of obesity (9.3 and 2.5- fold) in PON1192QQ children compared to PON1192RR children at ages two and five, respectively. Similar relationships were seen with BMI Z-scores at age two and waist circumference at age five. After adjusting for genetic ancestry in models of PON1 and BMI Z-score, effect estimates for PON1192 genotype changed 15% and 9% among two and five year old children, respectively, providing evidence of genetic confounding by population stratification. However even after adjustment for genetic ancestry, the trend of increased BMI Z-scores with increased number of PON1192 Q alleles remained. Our findings suggest that PON1 may play a role in obesity independent of genetic ancestry and that studies of PON1 and health outcomes, especially in admixed populations, should account for differences due to population stratification

The structure, energy, and electronic states of vacancies in Ge nanocrystals

The atomic structure, energy of formation, and electronic states of vacancies in H-passivated Ge nanocrystals are studied by density functional theory (DFT) methods. The competition between quantum self-purification and the free surface relaxations is investigated. The free surfaces of crystals smaller than 2 nm distort the Jahn-Teller relaxation and enhance the reconstruction bonds. This increases the energy splitting of the quantum states and reduces the energy of formation to as low as 1 eV per defect in the smallest nanocrystals. In crystals larger than 2 nm the observed symmetry of the Jahn-Teller distortion matches the symmetry expected for bulk Ge crystals. Near the nanocrystal's surface the vacancy is found to have an energy of formation no larger than 0.5 to 1.4 eV per defect, but a vacancy more than 0.7 nm inside the surface has an energy of formation that is the same as in bulk Ge. No evidence of the self-purification effect is observed; the dominant effect is the free surface relaxations, which allow for the enhanced reconstruction. From the evidence in this paper, it is predicted that for moderate sized Ge nanocrystals a vacancy inside the crystal will behave bulk-like and not interact strongly with the surface, except when it is within 0.7 nm of the surface.Comment: In Press at Phys. Rev.

CpG Methylation of a Silent Controlling Element in the Murine Avy Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation

Background: The viable yellow allele of agouti (A vy) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A vy allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between A vy mice indicates that the epigenetic state of the IAP is unstable in the germline. Principal Findings: We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of A vy phenotypes, does not increase the density of CpG methylation in the silent LTR. Conclusions: Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence A vy. The incomplete cytosine methylation we observe at the somatically silent A vy allele ma

Using DNA pools for genotyping trios

The genotyping of mother–father–child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies may reduce power, since it requires the genotyping of three individuals where only four independent haplotypes are involved. We describe here a method for genotyping a trio using two DNA pools, thus reducing the cost of genotyping trios to that of genotyping two individuals. Furthermore, we present extensions to the method that exploit the linkage disequilibrium structure to compensate for missing data and genotyping errors. We evaluated our method on trios from CEPH pedigree 66 of the Coriell Institute. We demonstrate that the error rates in the genotype calls of the proposed protocol are comparable to those of standard genotyping techniques, although the cost is reduced considerably. The approach described is generic and it can be applied to any genotyping platform that achieves a reasonable precision of allele frequency estimates from pools of two individuals. Using this approach, future trio-based association studies may be able to increase the sample size by 50% for the same cost and thereby increase the power to detect associations

Ancestry-related assortative mating in Latino populations

Examination of ancestry-informative genetic markers shows that Puerto Rican and Mexican populations have shown strong assortative mating that continues to this day

Dramatic age-related changes in nuclear and genome copy number in the nematode Caenorhabditis elegans

The nematode Caenorhabditis elegans has become one of the most widely used model systems for the study of aging, yet very little is known about how C. elegans age. The development of the worm, from egg to young adult has been completely mapped at the cellular level, but such detailed studies have not been extended throughout the adult lifespan. Numerous single gene mutations, drug treatments and environmental manipulations have been found to extend worm lifespan. To interpret the mechanism of action of such aging interventions, studies to characterize normal worm aging, similar to those used to study worm development are necessary. We have used 4′,6′-diamidino-2-phenylindole hydrochloride staining and quantitative polymerase chain reaction to investigate the integrity of nuclei and quantify the nuclear genome copy number of C. elegans with age. We report both systematic loss of nuclei or nuclear DNA, as well as dramatic age-related changes in nuclear genome copy number. These changes are delayed or attenuated in long-lived daf-2 mutants. We propose that these changes are important pathobiological characteristics of aging nematodes

Linguistic Factors Affecting Moraic Duration in Spontaneous Japanese

Japanese is often referred to as a mora-timed language (Ladefoged 1975): the mora has been described as the psychological prosodic unit in the spoken language, and it is the metric unit of traditional poetry (Bloch 1950). However, it is clear that mo- rae are not strictly isochronous units (Beckman 1982). Thus, experimental studies have focused on detecting compensation effects that make average mora durations more equal through the modulation of the inherent duration of the segments involved (Han 1962; Port, Al-Ani, Maeda 1980; Homma 1981; Hoequist 1983a; 1983b; Warner, Arai 2001). Kawahara (2017) used the Corpus of Spontaneous Japanese to verify whether the dura- tional compensation effect within a /CV/ mora occurs in natural speech, in addition to read speech in the lab. He observed a statistically significant compensation effect of /CV/ morae, in which vowel duration tends to vary in response to the duration of the preced- ing consonant. However, as the same author has pointed out, the compensation is not absolute because there are several linguistic factors that potentially affect segments’ duration profiles. This study will support the idea that moraic isochrony does not occur in spontaneous Japanese by presenting empirical data on how linguistic factors can considerably affect variation in the average duration of morae