DNA identification by pedigree likelihood ratio accommodating population substructure and mutations

DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the algorithms is explained, and several ways to reduce the complexity are introduced

Sensitivity and Specificity of Body Mass Index as a Definition of the Obesity Component of Metabolic Syndrome

Metabolic syndrome (MS) is a combination of risk factors that are associated with several chronic diseases. Its components (obesity, dyslipidemia, carbohydrate intolerance, hypertension, microalbumineria) are diverse, whose thresholds vary in different definitions of MS. For example, a World Health Organization (WHO) panel defined the obesity component of MS based on waist-hip ratio, or body mass index (BMI), while the National Cholesterol Education Program (NCEP) defined the obesity component of MS by waist circumference. Since BMI is the common measure of obesity in most epidemiological studies, this research addressed how accurately the obesity component of MS is captured by BMI alone. Data presented showed that in a population with high prevalence of obesity , the specificity of detecting the obesity component of MS by BMI alone is almost 100%, but the sensitivity is low (e.g., <50%). Individuals with high BMI generally have large waist-hip ratio and wide waist circumference, but the converse is not necessarily true. Consequently, centralized obesity (a risk factor for several chronic diseases) is not always captured by a high BMI alone

Concept, Measurement and Use of Acculturation in Health and Disease Risk Studies

Acculturation, a concept with its root in social science and cultural anthropology, is a process intimately related to health behavior and health status of minority populations in a multicultural society. This paper provides a brief review of the subject of acculturation as it relates to health research, showing that this concept has a potential to identify risk factors that underlie increased prevalence of chronic diseases, particularly in immigrant populations. A proper understanding of this is helpful in designing intervention programs to reduce the burden of such diseases and to increase the quality of life in such populations. The concept is defined with an outline of its history showing its evolution over time. Criteria for measuring acculturation are described to illustrate the need of accommodating its multidimensional features. Drawing examples from health research in US Hispanics, the role of acculturation on health behavior is discussed to document that the discordant findings are at least partially due to either use of incomplete dimensions of the concept, or not accounting for the dynamic aspect of its process. Finally, with illustration of a finding from a study among overweight Mexican American women of South Texas, a model of acculturation study is proposed that may be used in other immigrant populations undergoing the acculturation process

Genome-wide structural and evolutionary analysis of the P450 monooxygenase genes (P450ome) in the white rot fungus Phanerochaete chrysosporium : Evidence for gene duplications and extensive gene clustering

BACKGROUND: Phanerochaete chrysosporium, the model white rot basidiomycetous fungus, has the extraordinary ability to mineralize (to CO(2)) lignin and detoxify a variety of chemical pollutants. Its cytochrome P450 monooxygenases have recently been implied in several of these biotransformations. Our initial P450 cloning efforts in P. chrysosporium and its subsequent whole genome sequencing have revealed an extraordinary P450 repertoire ("P450ome") containing at least 150 P450 genes with yet unknown function. In order to understand the functional diversity and the evolutionary mechanisms and significance of these hemeproteins, here we report a genome-wide structural and evolutionary analysis of the P450ome of this fungus. RESULTS: Our analysis showed that P. chrysosporium P450ome could be classified into 12 families and 23 sub-families and is characterized by the presence of multigene families. A genome-level structural analysis revealed 16 organizationally homogeneous and heterogeneous clusters of tandem P450 genes. Analysis of our cloned cDNAs revealed structurally conserved characteristics (intron numbers and locations, and functional domains) among members of the two representative multigene P450 families CYP63 and CYP505 (P450foxy). Considering the unusually complex structural features of the P450 genes in this genome, including microexons (2–10 aa) and frequent small introns (45–55 bp), alternative splicing, as experimentally observed for CYP63, may be a more widespread event in the P450ome of this fungus. Clan-level phylogenetic comparison revealed that P. chrysosporium P450 families fall under 11 fungal clans and the majority of these multigene families appear to have evolved locally in this genome from their respective progenitor genes, as a result of extensive gene duplications and rearrangements. CONCLUSION: P. chrysosporium P450ome, the largest known todate among fungi, is characterized by tandem gene clusters and multigene families. This enormous P450 gene diversity has evolved by extensive gene duplications and intragenomic recombinations of the progenitor genes presumably to meet the exceptionally high metabolic demand of this biodegradative group of basidiomycetous fungi in ecological niches. In this context, alternative splicing appears to further contribute to the evolution of functional diversity of the P450ome in this fungus. The evolved P450 diversity is consistent with the known vast biotransformation potential of P. chrysosporium. The presented analysis will help design future P450 functional studies to understand the underlying mechanisms of secondary metabolism and oxidative biotransformation pathways in this model white rot fungus

Response to: Use of prior odds for missing persons identifications - authors' reply

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Use of prior odds for missing persons identifications

Identification of missing persons from mass disasters is based on evaluation of a number of variables and observations regarding the combination of features derived from these variables. DNA typing now is playing a more prominent role in the identification of human remains, and particularly so for highly decomposed and fragmented remains. The strength of genetic associations, by either direct or kinship analyses, is often quantified by calculating a likelihood ratio. The likelihood ratio can be multiplied by prior odds based on nongenetic evidence to calculate the posterior odds, that is, by applying Bayes' Theorem, to arrive at a probability of identity. For the identification of human remains, the path creating the set and intersection of variables that contribute to the prior odds needs to be appreciated and well defined. Other than considering the total number of missing persons, the forensic DNA community has been silent on specifying the elements of prior odds computations. The variables include the number of missing individuals, eyewitness accounts, anthropological features, demographics and other identifying characteristics. The assumptions, supporting data and reasoning that are used to establish a prior probability that will be combined with the genetic data need to be considered and justified. Otherwise, data may be unintentionally or intentionally manipulated to achieve a probability of identity that cannot be supported and can thus misrepresent the uncertainty with associations. The forensic DNA community needs to develop guidelines for objectively computing prior odds

Y-chromosome SNP haplotypes suggest evidence of gene flow among caste, tribe, and the migrant Siddi populations of Andhra Pradesh, South India

From observations of lack of haplotype sharing based on Y-chromosome specific short tandem repeat (STR) loci, previous reports suggested negligible gene flow among different geographic populations of India. Using Single Nucleotide Polymorphism (SNP) sites in combination with STRs, we observed evidence of haplotype sharing across caste-tribe boundaries in South India. We examined 27 SNPs in the non-recombining region of the Y chromosome to investigate gene flow in 204 individuals belonging to three caste groups (Vizag Brahmins, Peruru Brahmins, Kammas), three tribes (Bagata, Poroja, Valmiki) and an additional group (the Siddis) of African ancestry. Principal component and AMOVA analyses show that the between group component of variation is non-significant (P&gt;0.05), while that among populations within the caste and tribal groups is significant (P&lt;0.001). In particular, the Valmikis and Siddis are close to the caste groups. Of a total of 11 distinct SNP-haplotypes observed, the two tribal groups (Bagata and Poroja) lack the haplotypes H4, H4A, H5A and H16, which are seen in the caste groups. In contrast, all three tribal groups exhibit the Southeast Asian haplotype H11 that is absent in the caste populations. The presence of haplotypes H4, H5, H14, and H16 in the Siddis indicate that they have assimilated considerable non-African admixture. The evidence of haplotype sharing between castes and tribes is also found when the H14 lineage was further subdivided by five STR loci. We conclude that even though these SNP-based Y-haplotypes are able to distinguish the populations, gene flow in these South Indian populations is not as negligible as that inferred from other studies based on Y-specific short tandem repeat markers