A nation's genes for a cure to cancer: evolving ethical, social and legal issues regarding population genetic databases

The advent of the human genome sequence has focused research on understanding underlying genetic links to complex diseases such as cancer, asthma and heart disease. In the past few years, individual countries, such as Iceland, Estonia, Singapore and the United Kingdom, have created national databases of their citizens' DNA for comparative research. Most recently, an international consortium including Nigeria, Japan, China and the United States launched a $100 million project called the International HapMap to map the human genome according to haplotypes, blocks of DNA that contain genetic variation. Such population genetic databases present challenging ethical, social and legal issues, yet regulation of genetic information has developed sporadically, from region to region, without a consistent international standard. Without a clear understanding of the consequences of genetic research in terms of individual and community-wide discrimination and stigmatization, genetic databases raise concerns about the protection of genetic information. This Note provides a survey of the evolving landscape of population genetic databases as a legislative and public policy tool for national and international regulators. It compares different approaches to regulating the collection and use of population genetic databases in order to understand what areas of consensus are formulating a foundation for an international standard. As the first population genetics project that will span multiple countries for the collection of DNA, the International HapMap has the potential to become an influential standard for the protection of population genetic information. This Note highlights issues among the national databases and the HapMap project that raise ethical, social and legal concerns for the future and recommends further protections for both individual donors and community interests.     

Implications for DNA identification arising from an analysis of Australian forensic databases

Previous analyses of Australian samples have suggested that populations of the same broad racial group (Caucasian, Asian, Aboriginal) tend to be genetically similar across states. This suggests that a single national Australian database for each such group may be feasible, which would greatly facilitate casework. We have investigated samples drawn from each of these groups in different Australian states, and have quantified the genetic homogeneity across states within each racial group in terms of the "coancestry coefficient" F(ST). In accord with earlier results, we find that F(ST) values, as estimated from these data, are very small for Caucasians and Asians, usually <0.5%. We find that "declared" Aborigines (which includes many with partly Aboriginal genetic heritage) are also genetically similar across states, although they display some differentiation from a "pure" Aboriginal population (almost entirely of Aboriginal genetic heritage).     

A population genetic database of cat breeds developed in coordination with a domestic cat STR multiplex

A simple tandem repeat (STR) PCR-based typing system developed for the genetic individualization of domestic cat samples has been used to generate a population genetic database of domestic cat breeds. A panel of 10 tetranucleotide STR loci and a gender-identifying sequence tagged site (STS) were co-amplified in genomic DNA of 1043 individuals representing 38 cat breeds. The STR panel exhibits relatively high heterozygosity in cat breeds, with an average 10-locus heterozygosity of 0.71, which represents an average of 38 breed-specific heterozygosities for the 10-member panel. When the entire set of breed individuals was analyzed as a single population, a heterozygosity of 0.87 was observed. Heterozygosities obtained for the 10 loci range from 0.72 to 0.96. The power for genetic individualization of domestic cat samples of the multiplex is high, with a probability of match (p(m)) of 6.2E-14, using a conservative θ = 0.05.     

Sequence variation of new alleles at the short tandem repeat D19S253 locus

This paper reports the sequences of two new alleles identified in a population database study on the short tandem repeat D19S253 locus. A Portuguese Caucasian population and a Portuguese African population were studied. Forty-four selected alleles were sequenced and 11 different alleles were found. All the sequenced alleles shown to possess a simple tetranucleotide GATA repeat region structure. The two new alleles, alleles 6 and 16, follow the simple repeat pattern. During paternity investigation casework, 1028 meiosis were analyzed and five isolated genetic incompatibilities detected. In one case, a non-detectable allele with the used set of primers could be the explanation. In the other four cases, single-step mutations could be considered. The mutation rate obtained for this locus was 3.89 x 10(-3).     

Implication of population structure in the resolution of cattle stealing cases

Estimation of population subdivision using genetic markers shows that genetic differentiation in livestock and pet breeds is significantly higher than in human populations. Nevertheless, the influence of population substructure and sample size on match probability has not been extensively analyzed in domestic species. To evaluate the magnitude of the subpopulation effect on estimation of match probabilities in bovine robbery cases, we calculated and compared the match probabilities obtained from cattle breed databases using both real, adjudicated cases from the Buenos Aires Province (Argentina), as well as simulated data. While the Balding and Nichols' correction, when applied to the population database used in the case, produce a more conservative value favorable to the defendant, the match probabilities calculated using the simple product estimator produce a value favorable to the prosecution. We suggest an alternative procedure that can be used. The method consists of choosing the highest value from all match probabilities calculated from the database of each breed. This approach represents an intermediate and more accurate estimation of match probability, although it still produces a slight conservative value favorable to the defense.     

Criminal DNA databases: the European situation

In the last 5 years, a number of European countries have successfully introduced national databases holding the DNA profiles from suspected and convicted criminal offenders as well as from biological stain materials from unsolved crime cases. At present, DNA databases are fully or partially in operation in the UK, The Netherlands, Austria, Germany, Finland, Norway, Denmark, Switzerland and Sweden. Furthermore, in the other European countries, specific legislation will be enacted soon, or the introduction of such databases is being discussed to initiate a legislative process. Numerous differences exist regarding the criteria for a criminal offender to be included in the database, the storage periods and the possibility to remove database records, the possibility to keep reference samples from the offenders as long as their respective records are being held, and the role of judges in the process of entering a database record or to perform a database search. Nevertheless, harmonization has been achieved regarding the DNA information stored in national databases, and a European standard set of genetic systems has been recommended which is included either in part or completely in the DNA profiles of offenders and crime stains for all European databases. This facilitates the exchange of information from database records to allow the investigation of crime cases across national borders.     

Forensic genetic analysis of mitochondrial DNA hypervariable region I/II sequences: an expanded Korean population database

We have analyzed variation of the mitochondrial DNA (mtDNA) hypervariable segments I and II (HVS-I and HVS-II) in 185 randomly chosen individuals from Korea to provide an expanded and reliable Korean database. Combined sequence comparison of HVS-I and HVS-II led to the identification of 167 different haplotypes characterized by 154 variable sites. One hundred and fifty-one of the haplotypes were individual-specific, 14 were found in two individuals and 2 were found in three individuals. A pairwise comparison of the 185 HVS-I/II sequences found an average of 10.11 +/- 4.63 differences between individuals. The random match probability and gene diversity for the combined hypervariable regions were estimated at 0.66% and 0.9988, respectively. Analyzing the expanded database including three previously reported data sets and the present data using haplogroup-based comparisons and comparison with closely related sequences allowed errors to be detected and eliminated, thus considerably improving data quality. Sample division comparisons based on PhiST genetic distance measures revealed no significant population differentiation in the distribution of mtDNA sequence variations between the present data set and a database in The Scientific Working Group on DNA Analysis Methods (SWGDAM), but did indicate differences from other sets of data. Based on the results of mtDNA profiles, almost all of the mtDNA types studied here could be classified into subsets of haplogroups common in east Asia, and show that the Koreans possess lineages from both the southern and the northern haplogroup complexes of east Asian populations. The new data, combined with other mtDNA sequences, demonstrate how useful comparison with closely related mtDNA sequences can be for improving database quality, as well as providing haplotype information for forensic and population genetic analyses in the Korean population.     

Sequence characterization of microvariant alleles at DYS627 and DYS458

Y chromosome short tandem repeats (Y-STRs) have been widely used in genetic applications and forensic casework. Recently, we found two intermediate alleles, the DYS627 allele 24.1 and the DYS458 allele 15.3, from Chinese Han population. The two allelic variants have not been recorded by the YHRD database. We have examined the molecular structure of these allelic variants by Sanger sequencing. The results showed that this intermediate allele at DYS627 was confirmed as 24.1, the sequence of which showed a base “A” insertion in the 13th repeat unit, and the intermediate allele at DYS458 was confirmed as 15.3, the sequence of which showed a base “G” deletion in the 12th repeat unit. This may be important for individual identification and paternal kinship testing. Besides, more allelic variants detected can be enriched in the Y-STR database.     

Genetic data on 15 STRs in a population sample of religious minority of Old Believers residing in the northeastern Poland

This study provides a 15 STRs database for a population sample of Old Believers (n = 136) living in the northeastern Poland for the use as a highly discriminatory system of genetic markers in population studies and in personal identification. Significant differences revealed between the Old Believers and the autochthonous Poles by using RxC test as well as F(ST) and F(IS) estimates suggest a certain degree of genetic isolation of this religious minority.     

Average Probability that a "Cold Hit" in a DNA Database Search Results in an Erroneous Attribution

Abstract:  We consider a hypothetical series of cases in which the DNA profile of a crime-scene sample is found to match a known profile in a DNA database (i.e., a "cold hit"), resulting in the identification of a suspect based only on genetic evidence. We show that the average probability that there is another person in the population whose profile matches the crime-scene sample but who is not in the database is approximately 2( N  −  d ) p _A , where N is the number of individuals in the population, d is the number of profiles in the database, and p _A is the average match probability (AMP) for the population. The AMP is estimated by computing the average of the probabilities that two individuals in the population have the same profile. We show further that if a priori each individual in the population is equally likely to have left the crime-scene sample, then the average probability that the database search attributes the crime-scene sample to a wrong person is ( N  −  d ) p _A .     

中国鄂温克族DXS7423，DXS7424，DXS7132，DXS7133，DXS6804位点多态性的研究

目的以无关个体为研究对象,研究鄂温克族人群X染色体5个STR位点的遗传多态性,建立群体遗传数据库。方法用聚合酶链反应(PCR)、变性聚丙烯凝胶电泳和银染的方法,检测98名中国鄂温克族DXS7423,DXS7424,DXS7132,DXS7133,DXS6804位点的重复序列长度的变化。结果5个STR位点在鄂温克族群体均具有遗传多态性,χ2检验表明多态性分布符合Hardy-Weinberg平衡定律。结论中国鄂温克族X染色体5个STR基因座群体遗传数据资料,可用于法庭科学个体识别、亲子鉴定及其他人类学研究。     

The advent of DNA databanks: implications for information privacy

Genetic identification tests -- better known as DNA profiling -- currently allow criminal investigators to connect suspects to physical samples retrieved from a victim or the scene of a crime. A controversial yet acclaimed expansion of DNA analysis is the creation of a massive databank of genetic codes. This Note explores the privacy concerns arising out of the collection and retention of extremely personal information in a central database. The potential for unauthorized access by those not investigating a particular crime compels the implementation of national standards and stringent security measures.     

Haplotype data for the 12 RM Y-STR loci in a Syrian population

Researches with RM Y-STRs have shown that these loci provide substantially higher haplotype diversity and haplotype discrimination capacity in worldwide populations when compared with the YSTRs commonly used in genetic forensics. The aim of this study was to develop an allelic frequency database for the Syrian population living in Turkey in order to obtain population data of 12 RM Y-STRs. A total of 80 unrelated males from the Syrian population living in Turkey were typed with 12 RM Y-STRs loci: DYF387S1, DYF399S1, DYF404S1, DYS449, DYS518, DYS526a/b, DYS547, DYS570, DYS576, DYS612, DYS626 and DYS627. The highest GD was observed for the locus DYF399S1 (0.91), followed by loci DYS449 (0.86) and DYS518 (0.83). RM Y-STR haplotype diversity was found 1.00 in these samples. Based on the results of this study, the RM YSTR loci showed remarkable haplotype resolution power in the Syrian population, high genetic diversity and, therefore, demonstrating their usefulness in forensic identification cases.     

Testing for genetic structure in different urban Argentinian populations

Fifteen autosomal short tandem repeat (STR) markers (D3S1358, HUMTH01, D21S11, D18S51, PENTA E, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTA D, HUMvWA, D8S1179, HUMTPOX, FGA) were analyzed in 1734 individuals living in urban areas of cities from six different Argentinian provinces (Buenos Aires, Neuquén, Tucumán, La Pampa, San Luis, Santa Cruz) in order to determine if a common urban database could be used in Argentina for forensic purposes. Frequencies estimates, Hardy-Weinberg equilibrium (HWE), and other parameters of forensic interest were computed. Comparisons between the six populations, and with published data from one Native American population from Argentina and other urban populations from Argentina and Europe were also performed. Our results reveal evidences for population structure, both when testing for genetic differentiation and when comparing frequencies distributions between different pairs of populations. Therefore, caution should be taken when using a common pooled database with general forensic purposes in Argentina.     

DNA identification of skeletal remains by investigator’s intuition

In June 2006 a decapitated woman was found in a parking area of the motorway in the area of Prato (Florence). Since the body was beheaded and no victim’s documents or objects were present at the crime scene, identification at that time was impossible. However, DNA profile from woman’s bones were collected. In the same year (2003), a mother had reported her daughter's disappearance but the two events were not related at that time. About ten years later the mother’s DNA profile was finally acquired for a genetic identification of another girl’s body found in the Ferrara area. These genetic profiles were completely discordant. All these genetic comparisons were carried out on behalf of the prosecutors of the cities involved in the findings of the bodies and in the disappearance complaints, but due to the lack of a database the events remained disconnected. In January 2017, the head of the scientific police of Prato who had followed the investigation and questioned the mother of the missing girl found about ten years later, suggested to the magistrate to order the comparison of the mother's DNA with the genetic profile of the bones found in 2006. This comparison finally allowed the identification of the missing daughter.This story highlights the importance of having forensic DNA database to search for missing persons and how the investigator's intuition can play a key role in resolving criminal cases. In fact, databases of unknown bodies and relatives of missing persons were created in Italy as a part of national DNA database just at the beginning of 2018.     

论现代公共法律服务多元化规范体系建构

公共法律服务体系建设现代化的核心问题是满足人民群众追求美好生活日益增长的法律服务需求,为实现共同富裕发展目标提供全方位的法治保障。现代公共法律服务体系建设的地方立法例中,均集中体现出对公共法律服务基本概念和调整范围的反思与分歧,为此亟待厘清公共法律服务应然规范构造理论,这是未来形成公共法律服务全国统一立法的法学理论基础。公共法律服务专门立法在整个公共法律服务规范体系中具有纲领性地位,公共法律服务体系建设改革实践不仅具备基本服务与非基本服务二元结构架构特征,而且越来越多地呈现出多元和多维架构的本质特征。现有二元规范构造理论已经不能全面解释和解构现有的公共法律服务体系建设实践发展的全样本和多维度、多元化样态,只有建构多元化的现代公共法律服务规范体系才能根本解决现有公共法律服务地方立法例实践及理论研究中出现的关于基本概念、规范类型、规范属性、调整方式、权利属性等诸多基本争议,从而确定公共法律服务的权利义务主体、事项范围、模式与程序、标准与评价指标、监督管理等主要体系建构的基本规范要素,进而归纳整合公共法律服务立法规范构造的本质特征,为将来形成区域协同一体化立法或全国统一立法提供立法规范要素的基本构造理论支撑。     

云南怒族X染色体5个STR基因座遗传多态性

目的以云南怒族无关个体为研究对象,调查怒族群体DXS6804、DXS6799、DXS8378、DXS7130、DXS7132基因座的基因频率及基因型频率分布,建立群体遗传数据库。方法用聚合酶链反应(PCR)、变性聚丙烯酰胺凝胶电泳结合银染的方法,检测100名云南怒族个体X染色体上5个STR基因座的重复序列长度变化。结果云南怒族群体5个STR基因座具有遗传多态性,χ2检验表明多态性分布符合Hardy-Weinberg平衡定律。结论云南怒族群体DXS6804、DXS6799、DXS8378、DXS7130和DXS7132基因座,可用于法医学个体识别、亲子鉴定等研究。     

Online reference database of European Y-chromosomal short tandem repeat (STR) haplotypes

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.     

社会中间层——经济法理论研究的崭新进路

社会中间层是在内涵上涵盖社会自治组织、社会经济团体等概念的理论范畴,通过"政府——市场"二元结构向"政府——中间层——市场"三元结构的转型,其作为经济法新的调整对象为经济法实现协调国家经济运行的立法目的提供了广阔的理论前景。本文将重点阐述社会中间层对经济法理论创新、实体法和程序法实现机制的作用和基础理论构想。     

A new method for the evaluation of matches in non-recombining genomes: application to Y-chromosomal short tandem repeat (STR) haplotypes in European males

A 9-locus microsatellite framework (minimal haplotype), previously developed for forensic purposes so as to facilitate stain analysis, personal identification and kinship testing, has been adopted for the establishment of a large reference database of male European Y-chromosomal haplotypes. The extent of population stratification pertaining to this database, an issue crucial for its practical forensic application, was assessed through analysis of molecular variance (AMOVA) of the 20 regional samples included. Despite the notion of some significant haplotype frequency differences, which were found to correlate with known demographic and historic features of Europeans, AMOVA generally revealed a high level of genetic homogeneity among the populations analyzed. Owing to their high diversity, however, accurate frequency estimation is difficult for Y-STR haplotypes when realistic (i.e. moderately sized) datasets are being used. As expected, strong pair-wise and higher order allelic associations were found to exist between all markers studied, implying that haplotype frequencies cannot be estimated as products of allele frequencies. A new extrapolation method was therefore developed which treats haplotype frequencies as random variables and generates estimates of the underlying distribution functions on the basis of closely related haplotypes. This approach, termed frequency 'surveying', is based upon standard population genetics theory and can in principle be applied to any combination of markers located on the Y-chromosome or in the mitochondrial genome. Application of the method to the quality assured reference Y-STR haplotype database described herein will prove very useful for the evaluation of positive trace-donor matches in forensic casework.