The effect of linkage on the calculation of DNA match probabilities for siblings and half siblings

The loci in many forensic multiplexes are often selected to avoid linked loci. However as the multiplices used increase in the number of loci represented instances are occurring of loci that are loosely linked. As yet little attention has been paid to the likely consequence of this. We begin the process of developing formulae to give the match probability at two linked loci for full and half siblings. The methodology proceeds from the previously published joint IBD states for two linked loci [B.K. Suarez, J. Rice, T. Reich, The generalized sib pair IBD distribution: its use in the detection of linkage, Ann. Hum. Genet. Lond. 42 (1978) 87; J.K. Haseman, R.C. Elston, The investigation of linkage between a quantitative trait and a marker locus, Behav. Genet. 2 (1972) 3–19]. Our formulation has the drawback of assuming linkage equilibrium. This assumption may be tenable as a first order approximation. We hope to stimulate work on developing better treatments.     

Allele frequencies and haplotypes of eight Y-short tandem repeats in Bantu population living in Central Africa

Eight Y chromosome short tandem repeats (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385I/II) were used to assess haplotype distribution in non-selected, unrelated Bantu males living in Central Africa [N. Mathias, M. Bayes, C. Tyler-Smith, Highly informative compound haplotypes for the human Y chromosome, Hum. Mol. Genet. 3 (1994) 115-123; L. Roewer, J. Arnemann, N.K. Spurr, K.H. Grzeschik, J.T. Epplen, Simple repeat sequences on the human Y chromosome are equally polymorphic as their autosomal counterparts, Hum. Genet. 89 (1992) 389-394; P. De Knijff, M. Kayser, A. Caglia, D. Corach, N. Fretwel, C. Gehrig, G. Graziosi, F. Heidorn, S. Herrmann, B. Herzog, M. Hidding, K. Honda, M. Jobling, M. Krawczak, K. Leim, S. Meuser, E. Meyer, W. Oesterreich, A. Pandya, W. Parson, G. Penacino, A. Perez-Lezaun, A. Piccini, M. Prinz, C. Schmitt, P. M. Schneider, R. Szibor, J. Teifel-Greding, G. Weishold, L. Rower, Chromosome Y microsatellites: population genetic and evolutionary aspects, Int. J. Legal Med. 110 (1997) 134-149; M. Kayser, A. Caglia, D. Corach, N. Fretwel, C. Gehrig, G. Graziosi, F. Heidorn, S. Herrmann, B. Herzog, M. Hidding, K. Honda, M. Jobling, M. Krawczak, K. Leim, S. Meuser, E. Meyer, W. Oesterreich, A. Pandya, W. Parson, G. Penacino, A. Perez-Lezaun, A. Piccini, M. Prinz, C. Schmitt, P. M. Schneider, R. Szibor, J. Teifel-Greding, G. Weishold, P. de Knijff, L. Rower, Evaluation of Y chromosome STRs: a multicenter study, Int. J. Legal Med. 110 (1997) 125-133, 141-149]. One hundred and sixty-five full haplotypes were obtained from Bantu males. The most common haplotype (DYS19-15, DYS389I-13, DYS389II-30, DYS390-21, DYS391-10, DYS392-11, DYS393-13, DYS385I/II-15,17) was shared by 5.5% of individuals. In the Bantu population in Central Africa, the haplotype diversity and the discrimination capacity of Y-STR may be estimated at 99.14% and 0.5333, respectively.     

Updated allelic structures of the DXS10135 and DXS10078 STR loci

DXS10135 and DXS10078 are two highly polymorphic STR loci situated in two different linkage groups on the short arm of the human X chromosome. Both loci comprise complex tetrameric repeat units which may partially explain their high degree of polymorphism. DXS10135 is relatively well characterized and is included in a commercially available kit, while DXS10078 has not been well described. We sequenced a large number of alleles of both loci to try and understand the allelic variation and as a prelude to construct allelic ladders from cloned alleles. Our data show interesting features and should encourage other workers to use these loci in forensic genetic investigations.     

IBD法在堂表亲缘关系鉴定中的应用

目的 使用血缘一致性(identity by descent,IBD)法计算堂表亲缘关系的堂表关系指数(first cousin index,FCI)和累积堂表关系指数(combined first cousin index,CFCI),为IBD法鉴定两个个体是否具有堂表亲缘关系提供科学手段.方法 取124对堂表兄弟姐...     

A Test of Case Linkage Principles with Solved and Unsolved Serial Rapes

Case linkage involves identifying crime series on the basis of behavioral similarity and distinctiveness. Research regarding the behavioral consistency of serial rapists has accumulated; however, it has its limitations. One of these limitations is that convicted or solved crime series are exclusively sampled whereas, in practice, case linkage is applied to unsolved crimes. Further, concerns have been raised that previous studies might have reported inflated estimates of case linkage effectiveness due to sampling series that were first identified based on similar modus operandi (MO), thereby overestimating the degree of consistency and distinctiveness that would exist in naturalistic settings. We present the first study to overcome these limitations; we tested the assumptions of case linkage with a sample containing 1) offenses that remain unsolved, and 2) crime series that were first identified as possible series through DNA matches, rather than similar MO. Twenty-two series consisting of 119 rapes from South Africa were used to create a dataset of 7021 crime pairs. Comparisons of crime pairs that were linked using MO vs. DNA revealed significant, but small differences in behavioral similarity with MO-linked crimes being characterized by greater similarity. When combining these two types of crimes together, linked pairs (those committed by the same serial offender) were significantly more similar in MO behavior than unlinked pairs (those committed by two different offenders) and could be differentiated from them. These findings support the underlying assumptions of case linkage. Additional factors thought to impact on linkage accuracy were also investigated.     

What is the magnitude of the subpopulation effect?

The effect of population subdivision on estimated match probabilities has been raised [Nature 339 (1989) 501; Am. J. Hum. Genet. 48 (1991) 819; Science 254 (1991) 1921]. Previous work [J. Forensic Sci. 39 (1994) 319; J. Forensic Sci. 39 (1994) 988; Am. J. Hum. Genet. 55 (1994) 533] has compared product rule estimates from differing databases and found that the "subpopulation" error may be of the order of a factor of 10. This approach compares an estimate with an estimate. This paper uses simulation to extend these studies by allowing a comparison to a 'true match probability' and supports the conclusion that subpopulation effects are mild. In addition the performance of recommendations 4.1 and 4.2 of NRC II [National Research Council and C.O.D.F. Science, The Evaluation of Forensic DNA Evidence, National Academy Press, Washington, DC, 1996].     

Distribution of the HLA-DQA1 and polymarker alleles in the Basque population of Spain

HLA-DQA1 and polymarker (LDLR, GYPA, HBGG, D7S8, and GC) genotypic and allelic frequencies are determined for a population sample of 102 unrelated Basque individuals using PCR-based methodology. All six loci met Hardy-Weinberg expectations in at least two of the three analyses performed (HLA-DQA1 failed to meet Hardy-Weinberg requirements in the heterozygote deficiency test). Three linkage analysis programs (GDA, GENEPOP and LINKDOS) detected possible linkage disequilibrium between LDLR and HBGG and results from one (GDA) indicated a possible non-random association between HBGG and HLA-DQA1 as well. Allelic data for the six loci are compared to that previously established for other populations (18 for polymarker alone, 16 for polymarker plus HLA-DQA1) to determine homogeneity between the Basque sample and these groups. According to the results of G-tests based on these loci, the Tadjik, a nomadic Caucasian group from western Asia, and the Basque residents are the only sample populations surveyed that are homogenous with the Basque sample. Phylogenetic analysis places the Basque sample correctly within the Caucasian cluster.     

Microhaplotype loci are a powerful new type of forensic marker

Modern sequencing technology makes it possible to genotype polymorphisms with high throughput and high multiplexing. We have searched for and identified many loci with 2 or more SNPs within the expanse of a 200 bp single sequence run and show that when linkage disequilibrium is not complete these loci have multiple alleles detected as phase-known haplotypes. These microhaplotype loci (microhaps) are a powerful tool for individual identification, ancestry inference, and determining family/clan relationships.     

Genetic polymorphism of 14 non-CODIS STR loci for forensic use in southeast China population

We investigated 14 polymorphic STR loci (D1S2142, D2S1360, D3S1545, D7S1517, D10S2325, D12S391, D13S1492, D14S306, D15S659, D16S3253, D18S1270, D19S253, D20S470, D21S1437) which are not included in the standard sets of forensic loci (CODIS) in a sample of 216 unrelated healthy southeast Chinese individuals. The studied loci were highly informative and did not show departures from Hardy-Weinberg equilibrium. The accumulated powers of discrimination and power of exclusion for the 14 loci were 99.9999999999 and 99.999998%, respectively. No linkage was observed between the 14 loci and the traditional set of STR markers included in commercially available kits (the AmpFLSTR IdentifilerTM 15 System loci). We thus considered the studied 14 STRs are informative and when necessary, can be used as the candidate genetic markers in the study and application in genetics and forensic practice.     

Genetics and genomics of core short tandem repeat loci used in human identity testing

Over the past decade, the human identity testing community has settled on a set of core short tandem repeat (STR) loci that are widely used for DNA typing applications. A variety of commercial kits enable robust amplification of these core STR loci. A brief history is presented regarding the selection of core autosomal and Y-chromosomal STR markers. The physical location of each STR locus in the human genome is delineated and allele ranges and variants observed in human populations are summarized as are mutation rates observed from parentage testing. Internet resources for additional information on core STR loci are reviewed. Additional topics are also discussed, including potential linkage of STR loci to genetic disease-causing genes, probabilistic predictions of sample ethnicity, and desirable characteristics for additional STR loci that may be added in the future to the current core loci. These core STR loci, which form the basis for DNA databases worldwide, will continue to play an important role in forensic science for many years to come.     

67个X-SNP位点的分型检测和连锁不平衡检验

目的 筛选一组在中国汉族人群中具有法医学应用前景的X-SNP位点.方法 根据dbSNP和HapMap两个数据库提供的位点信息和频率数据从X染色体上筛选出67个候选X-SNP位点,采用多重PCR联合基质辅助激光解析电离飞行时间质谱技术检测中国汉族人群428名无关个体,获得67个候选X-SNP位点在中国汉族人群中的频率数据...     

Calculating the exclusion probability and paternity index for X-chromosomal loci in the presence of substructure

There has been recent interest in the use of X-chromosomal loci for forensic and relatedness testing casework, with many authors developing new X-linked short tandem repeat (STR) loci suitable for forensic use. Here we present formulae for two key quantities in paternity testing, the average probability of exclusion and the paternity index, which are suitable for X-chromosomal loci in the presence of population substructure.     

Results of collaborative study regarding the standardization of the Y-linked STR system DYS385 by the European DNA Profiling (EDNAP) group.

Y-chromosome linked short tandem repeat (STR) loci are inherited as a closely linked haplotype, which appears to remain stable in a given paternal lineage over many generations. In forensic cases, Y-linked STRs are particularly useful for the identification of human remains as well as in rape cases with mixed male/female stain samples. DYS385 is derived from tandemly duplicated segments of the Y chromosome thus giving rise to two fragments of variable length which do not behave like alleles but genotypes. The European DNA Profiling (EDNAP) group has carried out a collaborative exercise among 14 participating laboratories using DYS385 for typing of five unknown bloodstains and a control sample. Furthermore, population data from eight different European countries with samples sizes between 91 and 150 male individuals were collected. The results confirm previous observations that DYS385 is one of the most informative Y-linked STR loci. It could also be demonstrated that reproducible results can be obtained independently from the electrophoretic separation and detection methods used. Thus DYS385 may serve as a useful complementation to the routinely used autosomal STR systems in special cases.     

Autosomal microsatellite allele frequencies for a nationwide dataset from the Australian Caucasian sub-population

DNA profiling results presented in court must be accompanied by a statistical estimate of its evidential weight. In calculating such statistics, allele frequencies from the tested loci are required. This paper reports allele frequencies and the results of population genetic testing of datasets of autosomal microsatellite profiles from Australian Caucasian donors. In contrast to previous practice in Australia these data have been collated at the national level rather than at the State and Territory level. We consider that this national dataset could be used in forensic DNA casework throughout Australia as previously recommended by Ayres et al. [K.L. Ayres, J. Chaseling, D.J. Balding, Implications for DNA identification arising from an analysis of Australian forensic databases, Forensic Sci. Int. 129 (2002) 90-98].     

Validation of nine non-CODIS STR loci for forensic use in a population from Central Poland

The D7S1517, D3S1744, D12S391, D2S1360, D6S474, D8S1132, D5S2500, D10S2325 and D4S236613 are STR loci potentially useful for forensic purposes whose analysis has recently become facilitated by availability of a commercial kit. The purpose of the study was to evaluate the usefulness of these loci for forensic identification in a population of Central Poland. The distribution of alleles of the nine STRs was determined in sample of 353 unrelated individuals born in Central Poland and indices of forensic informativeness were calculated. The studied loci were highly informative and did not show departures from Hardy-Weinberg equilibrium. For the loci located on the same chromosomes (D2S1360, D3S1744 D4S2366, D5S2500, D7S1517, D8S1132, D12S391) as other loci commonly used for identification purposes (TPOX, D2S1338, D3S1358, FGA, D5S818, D7S820, D8S1179 and D12S391) appropriate pairwise analysis of linkage disequilibrium was performed. In all cases no statistically significant deviation from independence was found. We conclude that the studied STRs are informative and, when necessary, can be used to extend the results obtained with other STRs commonly analyzed for identification purposes, in particular the CODIS set.     

On identification problems requiring linked autosomal markers

This paper considers identification problems based on DNA marker data. The topics we discuss are general, but we will exemplify them in a simple context. There is DNA available from two persons. There is uncertainty about the relationship between the two individuals and a number of hypotheses describing the possible relationship is available. The task is to determine the most likely pedigree. This problem is fairly standard. However, there are some problems that cannot be solved using DNA from independently segregating loci. For example, the likelihoods for (i) grandparent–grandchild, (ii) uncle–niece and (iii) half-sibs coincide for such DNA data and so these relations cannot be distinguished on the basis of markers normally used for forensic identification problems: the likelihood ratio comparing any pair of hypotheses will be unity.Sometimes, but not in the examples we consider, other sources of DNA like mtDNA or sex chromosomes can help to distinguish between such equally likely possibilities. Prior information can likewise be of use. For instance, age information can exclude alternative (i) above and also indicate that alternative (iii) is apriori more likely than alternative (ii).More generally, the above problems can be solved using linked autosomal markers. To study the problem in detail and understand how linkage works in this regard, we derive an explicit formula for a pair of linked markers. The formula extends to independent pairs of linked markers. While this approach adds to the understanding of the problem, more markers are required to obtain satisfactory results and then the Lander–Green algorithm is needed. Simulation experiments are presented based on a range of scenarios and we conclude that useful results can be obtained using available freeware (MERLIN and R).The main message of this paper is that linked autosomal markers deserve greater attention in forensic genetics and that the required laboratory and statistical analyses can be performed based on existing technology and freeware.     

X—STR基因座的法医学应用研究进展

对X染色体的结构特征、遗传特征及其短串联重复序列（STR）基因座在法医学领域的研究历史、现状进行了综述。并分析了X染色体STR基因座在混合斑鉴定和复杂亲子关系鉴定中的应用,以及在法医学领域应用中应注意的问题．如单倍型和连锁不平衡现象等。     

Estimating the probability of identity in a random dog population using 15 highly polymorphic canine STR markers

Dog DNA-profiling is becoming an important supplementary technology for the investigation of accident and crime, as dogs are intensely integrated in human social life. We investigated 15 highly polymorphic canine STR markers and two sex-related markers of 131 randomly selected dogs from the area around Innsbruck, Tyrol, Austria, which were co-amplified in three PCR multiplex reactions (ZUBECA6, FH2132, FH2087Ua, ZUBECA4, WILMSTF, PEZ15, PEZ6, FH2611, FH2087Ub, FH2054, PEZ12, PEZ2, FH2010, FH2079 and VWF.X). Linkage testing for our set of marker suggested no evidence for linkage between the loci. Heterozygosity (HET), polymorphism information content (PIC) and the probability of identity (P((ID)theoretical), P((ID)unbiased), P((ID)sib)) were calculated for each marker. The HET((exp))-values of the 15 markers lie between 0.6 (VWF.X) and 0.9 (ZUBECA6), P((ID)sib)-values were found to range between 0.49 (VWF.X) and 0.28 (ZUBECA6). Moreover, the P((ID)sib) was computed for sets of loci by sequentially adding single loci to estimate the information content and the usefulness of the selected marker sets for the identification of dogs. The estimated P((ID)sib) value of all 15 markers amounted to 8.5 x 10(-8). The presented estimations turned out to be a helpful approach for a reasonable choice of markers for the individualisation of dogs.     

常染色体STR遗传标记在同胞鉴定中的应用

目的 探讨常染色体STR遗传标记用于鉴定两个体同胞关系的可行性。方法 用Power Plex~(TM)16体系15个STR基因座检测150对同胞个体和150对无关个体,ITO法计算同胞关系指数(PI_(FS))与同胞关系概率(W_(FS)),并比较两组W_(FS)值及两个体间等位基因匹配情况的差异,对前者进行组间差异的x~2检验。结果 100对(66.67％)同胞个体的W_(FS)大于0.9995;无关个体W_(FS)均小于0.8,其中100对(66.67％)W_(FS)小于0.27。同胞个体两个体间等位基因全相同的基因座个数为1～10个不等,平均5.49个,无关个体0～5个不等,平均1.33个;等位基因全不同的基因座个数,同胞个体0～6个不等,平均1.66个,无关个体2～11个不等,平均6.57个;等位基因半相同的基因座个数,同胞个体3～13个不等,平均7.85个,而无关个体1～13个不等,平均7.11个。经x~2检验,同胞个体和无关个体间全相同和全不同的基因座数差异均有极显著意义(P<0.001),半相同的基因座数差异无显著意义(P>0.05)。结论 PowerPlex~(TM)16体系可用于鉴定同胞关系。当两个体全不同基因座个数大于或等于6个,或全相同基因座数为0时,提示为无关个体;当两个体全不同基因座个数小于或等于1个,或全相同基因座数大于或等于6个时,提示为同胞。     

The linking of burglary crimes using offender behaviour: Testing research cross‐nationally and exploring methodology

Purpose. The current study tests whether existing behavioural case linkage findings from the United Kingdom (UK) will replicate abroad with a sample of residential burglaries committed in Finland. In addition, a previously discussed methodological issue is empirically explored. Methods. Seven measures of behavioural similarity, geographical proximity, and temporal proximity are calculated for pairs of burglary crimes committed by 117 serial burglars in Finland. The ability of these seven measures to distinguish between pairs of crimes committed by the same offender (linked pairs) and different offenders (unlinked pairs) is tested using logistic regression and receiver operating characteristic (ROC) analysis. Two methodologies for forming the unlinked pairs are compared; one representing the ‘traditional’ approach used by research and, the other, a new approach that represents a potentially more realistic and statistically sound approach to testing case linkage. Results. A wider range of offender behaviours were able to distinguish between linked and unlinked crime pairs in the current Finnish sample than in previous UK‐based research. The most successful features were the kilometre‐distance between crimes (the intercrime distance), the number of days separating offences (temporal proximity), and a combination of target, entry, internal, and property behaviours (the combined domain). There were no statistically significant differences between the two methodological approaches. Conclusions. The current findings demonstrate that a wider range of offender behaviours can be used to discriminate between linked and unlinked residential burglary crimes committed in Finland than in the UK. The use of a more realistic and statistically sound methodology does not lead to substantial changes in case linkage findings.