Kinship index variations among populations and thresholds for familial searching

Current familial searching strategies are developed primarily based on autosomal STR loci, since most of the offender profiles in the forensic DNA databases do not contain Y-STR or mitochondrial DNA data. There are generally two familial searching methods, Identity-by-State (IBS) based methods or kinship index (KI) based methods. The KI based method is an analytically superior method because the allele frequency information is considered as opposed to solely allele counting. However, multiple KIs should be calculated if the unknown forensic profile may be attributed to multiple possible relevant populations. An important practical issue is the KI threshold to select for limiting the list of candidates from a search. There are generally three strategies of setting the KI threshold for familial searching: (1) SWGDAM recommendation 6; (2) minimum KI≥KI threshold; and (3) maximum KI≥KI threshold. These strategies were evaluated and compared by using both simulation data and empirical data. The minimum KI will tend to be closer to the KI appropriate for the population of which the forensic profile belongs. The minimum KI≥KI threshold performs better than the maximum KI≥KI threshold. The SWGDAM strategy may be too stringent for familial searching with large databases (e.g., 1 million or more profiles), because its KI thresholds depend on the database size and the KI thresholds of large databases have a higher probability to exclude true relatives than smaller databases. Minimum KI≥KI threshold strategy is a better option, as it provides the flexibility to adjust the KI threshold according to a pre-determined number of candidates or false positive/negative rates. Joint use of both IBS and KI does not significantly reduce the chance of including true relatives in a candidate list, but does provide a higher efficiency of familial searching.     

Effects of subpopulation structure on probability calculations of DNA profiles from forensic PCR analysis

DNA typing for forensic identification is a two-step process. The first step involves determining the profiles of samples collected at the crime scene and comparing them with the profiles obtained from suspects and the victims. In the case of a match that includes the suspect as the potential source of the material collected at the crime scene, the last step in the process is to answer the question, what is the likelihood that someone in addition to the suspect could match the profile of the sample studied? This likelihood is calculated by determining the frequency of the suspect's profile in the relevant population databases. The design of forensic databases and the criteria for comparison has been addressed by the NRC report of 1996 (National Research Council, 1996). However, the fact that geographical proximity, migrational patterns, and even cultural and social practices have effects on subpopulation structure establishes the grounds for further study into its effects on the calculation of probability of occurrence values. The issue becomes more relevant in the case of discrete polymorphic markers that show higher probability of occurrence in the reference populations, where several orders of magnitude difference between the databases may have an impact on the jury. In this study, we calculated G values for all possible pairwise comparisons of allelic frequencies in the different databases from the races or subpopulations examined. In addition, we analyzed a set of 24 unrelated Caucasian, 37 unrelated African-American, and 96 unrelated Sioux/Chippewa individuals for seven polymorphic loci (DQA1, LDLR, GYPA, HBGG, D7S8, GC, and D1S80). All three sets of individuals where sampled from Minnesota. The probability of occurrence for all seven loci were calculated with respect to nine different databases: Caucasian, Arabic, Korean, Sioux/Chippewa, Navajo, Pueblo, African American, Southeastern Hispanic, and Southwestern Hispanic. Analysis of the results demonstrated marked differences in the probabilities of occurrence when individuals were compared to the different populations and subpopulation databases. The possible genetic and forensic consequences of subpopulation structure on probability calculations are discussed.     

铜川汉族人群38个Y-STR基因座多态性调查

Y染色体上的短串联重复序列（Y chromosome short tandem repeats, Y-STRs）在法医鉴定,尤其是混合斑中男性成分的检测分析和家系排查中具有重要作用。随着Y-STR试剂盒的不断推出和数据库的建立,国内外针对不同地区和群体的Y-STR多态性研究日益增多,而有关铜川汉族Y-STR研究鲜有报道。基于此,采用YfilerTM Platinum复合扩增试剂盒对陕西铜川汉族669名无关男性个体进行38个Y-STR基因座遗传多态性调查,并探索铜川地区汉族与其他群体之间的遗传关系。调查共检出657种单倍型,单倍型多样性和识别能力分别为0.999 937 345和0.982 1。38个Y-STR基因座共检出428个等位基因,基因多样性值在0.108 9（DYS645）~0.969 9（DYS385）。群体遗传分析中,多维尺度分析（multi-dimensional scaling, MDS）和系统发育树分析结果显示铜川汉族与其他地区的汉族群体遗传距离更近。综上,研究结果中38个Y-STR基因座在铜川汉族群体中具有较高的遗传多态性,适合铜川地区法庭科学应用。     

The effect of close relatives on unsupervised Bayesian clustering algorithms in population genetic structure analysis

The inference of population genetic structures is essential in many research areas in population genetics, conservation biology and evolutionary biology. Recently, unsupervised Bayesian clustering algorithms have been developed to detect a hidden population structure from genotypic data, assuming among others that individuals taken from the population are unrelated. Under this assumption, markers in a sample taken from a subpopulation can be considered to be in Hardy-Weinberg and linkage equilibrium. However, close relatives might be sampled from the same subpopulation, and consequently, might cause Hardy-Weinberg and linkage disequilibrium and thus bias a population genetic structure analysis. In this study, we used simulated and real data to investigate the impact of close relatives in a sample on Bayesian population structure analysis. We also showed that, when close relatives were identified by a pedigree reconstruction approach and removed, the accuracy of a population genetic structure analysis can be greatly improved. The results indicate that unsupervised Bayesian clustering algorithms cannot be used blindly to detect genetic structure in a sample with closely related individuals. Rather, when closely related individuals are suspected to be frequent in a sample, these individuals should be first identified and removed before conducting a population structure analysis.     

The Influence of Relatives on the Efficiency and Error Rate of Familial Searching

We investigate the consequences of adopting the criteria used by the state of California, as described by Myers et al. (2011), for conducting familial searches. We carried out a simulation study of randomly generated profiles of related and unrelated individuals with 13-locus CODIS genotypes and YFiler® Y-chromosome haplotypes, on which the Myers protocol for relative identification was carried out. For Y-chromosome sharing first degree relatives, the Myers protocol has a high probability () of identifying their relationship. For unrelated individuals, there is a low probability that an unrelated person in the database will be identified as a first-degree relative. For more distant Y-haplotype sharing relatives (half-siblings, first cousins, half-first cousins or second cousins) there is a substantial probability that the more distant relative will be incorrectly identified as a first-degree relative. For example, there is a probability that a first cousin will be identified as a full sibling, with the probability depending on the population background. Although the California familial search policy is likely to identify a first degree relative if his profile is in the database, and it poses little risk of falsely identifying an unrelated individual in a database as a first-degree relative, there is a substantial risk of falsely identifying a more distant Y-haplotype sharing relative in the database as a first-degree relative, with the consequence that their immediate family may become the target for further investigation. This risk falls disproportionately on those ethnic groups that are currently overrepresented in state and federal databases.     

Forensic DNA and bioinformatics

The field of forensic science is increasingly based on biomolecular data and many European countries are establishing forensic databases to store DNA profiles of crime scenes of known offenders and apply DNA testing. The field is boosted by statistical and technological advances such as DNA microarray sequencing, TFT biosensors, machine learning algorithms, in particular Bayesian networks, which provide an effective way of evidence organization and inference. The aim of this article is to discuss the state of art potentialities of bioinformatics in forensic DNA science. We also discuss how bioinformatics will address issues related to privacy rights such as those raised from large scale integration of crime, public health and population genetic susceptibility-to-diseases databases.     

Forensic characteristic and population structure dissection of Shaanxi Han population in the light of diallelic deletion/insertion polymorphism data

The genetic polymorphisms of diallelic deletion/insertion polymorphic (DIP) loci in the Shaanxi Han population are still not clearly characterized. Herein, allele frequencies and forensic application efficiencies for 30 diallelic DIP loci were investigated in 506 unrelated healthy Han individuals from Chinese Shaanxi province. Based on population data of the same 30 diallelic DIP loci, the genetic differentiations, hierarchical clustering relationships and population architectures among Shaanxi Han and other 50 populations were further dissected through genetic and bioinformatics analyses. Results indicated that most of the 30 diallelic DIP loci were relatively high polymorphisms in the Shaanxi Han population; and there were the genetically intimate relationships between Shaanxi Han and the East Asian populations. In summary, this study provided significant insights into genetic background of Shaanxi Han population, and the multiplex amplification of these 30 diallelic DIP loci was appropriate for forensic individual identification and population genetic research in Shaanxi Han population.     

Rigorous Training of Dogs Leads to High Accuracy in Human Scent Matching-To-Sample Performance

Human scent identification is based on a matching-to-sample task in which trained dogs are required to compare a scent sample collected from an object found at a crime scene to that of a suspect. Based on dogs’ greater olfactory ability to detect and process odours, this method has been used in forensic investigations to identify the odour of a suspect at a crime scene. The excellent reliability and reproducibility of the method largely depend on rigor in dog training. The present study describes the various steps of training that lead to high sensitivity scores, with dogs matching samples with 90% efficiency when the complexity of the scents presented during the task in the sample is similar to that presented in the in lineups, and specificity reaching a ceiling, with no false alarms in human scent matching-to-sample tasks. This high level of accuracy ensures reliable results in judicial human scent identification tests. Also, our data should convince law enforcement authorities to use these results as official forensic evidence when dogs are trained appropriately.     

A likelihood ratio approach for identifying three-quarter siblings in genetic databases

The detection of family relationships in genetic databases is of interest in various scientific disciplines such as genetic epidemiology, population and conservation genetics, forensic science, and genealogical research. Nowadays, screening genetic databases for related individuals forms an important aspect of standard quality control procedures. Relatedness research is usually based on an allele sharing analysis of identity by state (IBS) or identity by descent (IBD) alleles. Existing IBS/IBD methods mainly aim to identify first-degree relationships (parent–offspring or full siblings) and second degree (half-siblings, avuncular, or grandparent–grandchild) pairs. Little attention has been paid to the detection of in-between first and second-degree relationships such as three-quarter siblings (3/4S) who share fewer alleles than first-degree relationships but more alleles than second-degree relationships. With the progressively increasing sample sizes used in genetic research, it becomes more likely that such relationships are present in the database under study. In this paper, we extend existing likelihood ratio (LR) methodology to accurately infer the existence of 3/4S, distinguishing them from full siblings and second-degree relatives. We use bootstrap confidence intervals to express uncertainty in the LRs. Our proposal accounts for linkage disequilibrium (LD) by using marker pruning, and we validate our methodology with a pedigree-based simulation study accounting for both LD and recombination. An empirical genome-wide array data set from the GCAT Genomes for Life cohort project is used to illustrate the method.Subject terms: Genetic markers, Population genetics     

东亚人群毛干蛋白中单氨基酸多态性检测方法建立与个体识别应用

目的 毛干是案件现场常见的生物物证，目前缺少有效的个体识别方法而未能在案件调查和法庭诉讼中发挥作用。毛干蛋白质组中的单氨基酸多态性（SAP）蕴含着个体遗传差异信息，可应用于个体识别。方法 为研究毛干物证SAP个体差异，本文使用离子液体对12份2 cm长的毛干样本（6人，每人2根）经过前处理后，进行LC-MS/MS质谱检测，分析毛干中的蛋白质组成。然后利用自建的东亚人群SAP蛋白质序列数据库，对质谱数据进行搜库分析，依据自建的SAP与SNP对应注释表信息，推导出SAP对应的nsSNP分型，并且与外显子测序nsSNP结果比较，进而验证SAP检测的准确性。最后，利用验证准确的SAP分型进行随机匹配概率的计算。结果 12份样品共计获得321个SAP，每个样本平均为（131±17）个。6人的随机匹配概率数值范围为1.4×10^-4~1.0×10^-9。结论 本文建立了东亚人群毛干蛋白中SAP检测方法，并验证了个体识别应用的能力，为法庭科学中毛干个体识别提供了有力的工具和新的思路。     

Validation of 4 type-STR analysis for identification of 50 Korean

Short tandem repeat (STR) analysis provides genetic fingerprinting of individuals and is an indispensable technique for forensic human identification. Recently, this technique has been used in social areas, such as the identification of The Korean War, descendants of national merit, and missing children. STR analysis is performed by analyzing iteration number of repeating bases in the human genome, and currently FBI provides the Combined DNA Index System (CODIS) based on DNA databases. Among them, we used the autosomal short tandem repeats of loci D13S317, D16S539, D21S11, and amelogenin to validate this technique for identification. The samples were collected from unrelated 50 Korean individuals, and 4 STR loci of these samples were analyzed by ABI 3130 genetic analyzer. We demonstrated that 47 samples out of 50 were classified completely with only 4 STR markers, and perfect sex identification could be accomplished with amelogenin analysis.     

Karl Popper,Forensic Science,and Nested Codes

This paper utilizes the framework of Karl Popper’s 3-world ontology to make the case that forensic science is a specialized coding system that establishes meaningful connections between the world of biology (world 1) and the world of human society (world 3). Forensic science is a cross-disciplinary endeavor that uses scientific methods to determine what transpired in a crime so the legal system can determine how to prosecute the offender(s). On a Popperian analysis of forensic science, world 1 consists of evidence gathered at the crime scene, which enables investigators to develop a detailed reconstruction of the incident for consideration under the legal and ethical codes of society, which are products of world 3. Understanding forensic science in this way serves two purposes: first, it extends Marcello Barbieri’s code biology into the realm of philosophical considerations in science, law and ethics; and second, it situates forensic science within the larger context of debates in contemporary philosophy of science.     

陕西渭南地区汉族人群17个Y-STR基因座多态性及遗传关系分析

调查陕西渭南地区汉族群体17个Y-STR基因座的多态性,探讨其群体遗传学及法医学应用价值。应用Y-fi ler荧光标记复合扩增系统,对413名陕西渭南地区汉族无关男性个体17个Y-STR基因座进行复合扩增,用ABI3130遗传分析仪进行基因分型,计算各基因座的群体遗传学参数,并结合已经发表的其他10个群体相应基因座的单倍型资料,分析各群体间的遗传距离。413名陕西渭南汉族个体共检出405种单倍型,其中397种单倍型仅出现1次,单倍型多样性达0.9999,基因多样性(GD)为0.4130(DYS391)~0.9734(DYS385a/b),累计GD值为0.9999。遗传距离分析提示,陕西渭南汉族与辽宁满族的遗传距离最小(0.00110),与青海藏族的遗传距离最大(0.22333)。结果表明,17个Y-STR基因座在陕西渭南汉族群体中具有丰富的遗传多态性和较高的非父排除能力,在法医学和人类群体遗传学研究中具有重要价值。     

Forensic applications of DNA fingerprinting

In many ways, DNA profiling technology is very similar to the conventional techniques used for forensic identification. As with, for example, blood grouping techniques, the molecular characteristics of the scene of crime sample may be determined and compared with those of the scene of reference samples from suspects and victim. If the molecular characteristics of the crime sample and the suspect are different, then they cannot be from the same person, whereas if they match, then the possibility remains that they may be from a single source. Similar material, such as blood or semen stains, may be used for both biochemical and genetic tests, and the main applications of identification and relationship testing are shared by both techniques. At this point, the similarity ends; DNA profiling has the following characteristics:

1. It is more sensitive, being able to generate sound data from only a tiny amount of even partially degraded biological material.
2. It is capable of resolving mixtures of semen or tissue from up to several individuals.
3. It has a far greater power of discrimination between individuals—sometimes up to 1 millionfold higher than conventional techniques.
4. It provides considerably more information on the nature of relationships, particularly in cases of incest.

As such, the technique represents a quantum leap in forensic identification and relationship testing.     

基于毛干蛋白质组的族群推断技术的建立与验证

毛干是一种案件现场常见的生物物证,由于核DNA含量极少且高度降解,难以采用现有的短串联重复序列(short tandem repeat,STR)检验方法进行个人识别鉴定,目前仅使用线粒体DNA检验进行母系亲缘关系的判定,利用率非常低.毛干中蛋白质非常稳定,而且具有遗传多态性,表现为基因组中的非同义单核苷酸多态性(non-synonymous single nucleotide polymorphisms,ns SNPs),转录翻译后形成蛋白质序列中的单氨基酸多态性(single amino acid polymorphisms,SAPs).充分利用毛干蛋白质中蕴含的遗传信息,为案件提供线索和证据,是实际公安业务的迫切需求,具有重要的应用价值.本文选取了104份中国汉族的毛干样本进行蛋白质组的检测,共获得了703个SAP位点,位于460个蛋白质上,共推导出552个nsSNP位点.进一步筛选在所有样本中检出率超过15%的位点,获得了88个nsSNP位点,使用毛干样本对应的口腔拭子DNA对88个ns SNP位点进行一代测序验证.为评估发现的nsSNP位点对于人群的区分能力,以千人数据库(1 000 Genome Project)为参考数据库,采用聚类分析和群体匹配概率等方法对检测的19份毛干样本进行人群来源推断.结果显示,通过检测毛干蛋白质组中的ns SNP可以实现东亚、欧洲、非洲三大洲际人群的区分.     

Fixed-bin analysis for statistical evaluation of continuous distributions of allelic data from VNTR loci, for use in forensic comparisons.

The detection of DNA polymorphisms by RFLP analysis is having a major impact on identity testing in forensic science. At present, this approach is the best effort a forensic scientist can make to exclude an individual who has been falsely associated with an evidentiary sample found at a crime scene. When an analysis fails to exclude a suspect as a potential contributor of an evidentiary sample, a means should be provided to assess suitable weight to the putative match. Most important, the statistical analysis should not place undue weight on a genetic profile derived from an unknown sample that is attributed to an accused individual. The method must allow for limitations in conventional agarose-submarine-gel electrophoresis and Southern blotting procedure, limited sample population data, possible subpopulation differences, and potential sampling error. A conservative statistical method was developed based on arbitrarily defined fixed bins. This approach permits classification of continuous allelic data, provides for a simple and portable data-base system, and is unlikely to underestimate the frequency of occurrence of a set of alleles. This will help ensure that undue weight is not placed on a sample attributed to an accused individual.     

Genotypic probabilities for pairs of inbred relatives

Expressions for the joint genotypic probabilities of two related individuals are used in many population and quantitative genetic analyses. These expressions, resting on a set of 15 probabilities of patterns of identity by descent among the four alleles at a locus carried by the relatives, are generally well known. There has been recent interest in special cases where the two individuals are both related and inbred, although there have been differences among published results. Here, we return to the original 15-probability treatment and show appropriate reductions for relatives when they are drawn from a population that itself is inbred or when the relatives have parents who are related. These results have application in affected-relative tests for linkage, and in methods for interpreting forensic genetic profiles.     

Analysis of Human Mitochondrial DNA Polymorphisms in the Japanese Population

The highly polymorphic nature and high amplification efficiency of mitochondrial DNA (mtDNA) is valuable for the analysis of biological evidence in forensic casework, such as the identification of individuals and assignment of race/ethnicity. To be useful, a mtDNA polymorphism database for the Japanese population requires an understanding of the range of haplotype variation and phylogenies of mtDNA sequences. To extend current knowledge on the haplotypes in the Japanese population, this study defines new lineages and provides more detail about some of those previously described. We compared the hypervariable regions (HVRs) of 270 healthy, unrelated Japanese individuals and demonstrated 192 haplotypes. Combining HVR1 and HVR2, the genetic diversity was 0.9935, thus providing a high level of identification capability. Haplogroup status was defined for 160 individuals using HVR1, HVR2, and particular coding region polymorphisms; these individuals belonged to 94 haplotypes, four of which were new lineages. The complete mtDNA sequence was also determined from seven individuals.     

D1S80 single-locus discrimination among African populations

The highly polymorphic D1S80 locus has no known genetic function. However, this variable number of tandem repeats (VNTR) locus has been highly valuable in forensic identification. In this study we report the allele and genotype frequencies of five African populations (Benin, Cameroon, Egypt, Kenya, and Rwanda), which can be used as databases to help characterize populations and identify individuals. The allele frequencies were used to infer genetic associations through phylogenetic, principal component, and G test statistical analyses. Compliance with Hardy-Weinberg equilibrium expectations was determined as were F(ST) estimates, theta p values, and power of discrimination assessment for each population. Our analyses of 28 additional populations demonstrate that the D1S80 locus alone can be used to discriminate geographic and ethnic groups. We have generated databases useful for human identification and phylogenetic studies.     

Etiological overlap between obsessive‐compulsive disorder and anorexia nervosa: a longitudinal cohort,multigenerational family and twin study

Obsessive‐compulsive disorder (OCD) often co‐occurs with anorexia nervosa (AN), a comorbid profile that complicates the clinical management of both conditions. This population‐based study aimed to examine patterns of comorbidity, longitudinal risks, shared familial risks and shared genetic factors between OCD and AN at the population level. Participants were individuals with a diagnosis of OCD (N=19,814) or AN (N=8,462) in the Swedish National Patient Register between January 1992 and December 2009; their first‐, second‐ and third‐degree relatives; and population‐matched (1:10 ratio) unaffected comparison individuals and their relatives. Female twins from the population‐based Swedish Twin Register (N=8,550) were also included. Females with OCD had a 16‐fold increased risk of having a comorbid diagnosis of AN, whereas males with OCD had a 37‐fold increased risk. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for a later diagnosis of AN (risk ratio, RR=3.6), whereas individuals first diagnosed with AN had an even greater risk for a later diagnosis of OCD (RR=9.6). These longitudinal risks were about twice as high for males than for females. First‐ and second‐degree relatives of probands with OCD had an increased risk for AN, and the magnitude of this risk tended to increase with the degree of genetic relatedness. Bivariate twin models revealed a moderate but significant degree of genetic overlap between self‐reported OCD and AN diagnoses (r_a=0.52, 95% CI: 0.26‐0.81), but most of the genetic variance was disorder‐specific. The moderately high genetic correlation supports the idea that this frequently observed comorbid pattern is at least in part due to shared genetic factors, though disorder‐specific factors are more important. These results have implications for current gene‐searching efforts and for clinical practice.