Crowdsourced and crowdfunded: the future of forensic DNA?

ABSTRACT

Forensic DNA analysis is dependent on comparing the known and the unknown. Expand the number of known profiles, and the likelihood of a successful match increases. Forensic use of DNA is moving towards comparing samples of unknown origin with publicly available genetic data, such as the records held by genetic genealogy providers. Use of forensic genetic genealogy has yielded a number of recent high-profile successes but has raised ethical and privacy concerns. Navigating family trees is complex, even more so when combined with a comparison of genetic relationships. This intelligence-gathering process has led to occasional false leads, and its use also risks a public backlash, similar to concerns over Cambridge Analytica. A cautious approach to use of this technique is therefore warranted.     

The ancestry of spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) in South Africa

Comprehensive genealogical investigations have been undertaken in eight families in the Afrikaans-speaking community of South Africa, in which at least one person had spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL). All eight families had ancestral links with two females. These women had multiple marriages and cohabitations during the late 17th and early 18th centuries and they were 12 generations removed from the affected individuals. The identification of these common progenitors confirmed the syndromic homogeneity of SEMDJL in South Africa and permitted recognition of numerous obligate heterozygotes, thus facilitating biomolecular investigations of the basic defect.     

Genealogies of recovery: The framing of therapeutic ambitions

The notion of recovery has become prominent in mental healthcare discourse in the UK, but it is often considered as if it were a relatively novel notion, and as if it represented an alternative to conventional treatment and intervention. In this paper, we explore some of the origins of the notion of recovery in the early 20th century in movements such as Alcoholics Anonymous and Recovery Inc. Whilst these phenomena are not entirely continuous with recovery in the present day, some important antecedents of the contemporary notion can be detected. These include the focus on the sufferers’ interior space as a key theatre of operations and the reinforcement and consolidation of medical ways of seeing the condition without any immediate medical supervision of the actors being necessary. This has resonance with many contemporary examples of recovery in practice where the art of living with a mental health condition is emphasised without the nature of the psychopathological condition itself being challenged.     

Optimized variant calling for estimating kinship

One of the fundamental goals of forensic genetics is sample attribution, i.e., whether an item of evidence can be associated with some person or persons. The most common scenario involves a direct comparison, e.g., between DNA profiles from an evidentiary item and a sample collected from a person of interest. Less common is an indirect comparison in which kinship is used to potentially identify the source of the evidence. Because of the sheer amount of information lost in the hereditary process for comparison purposes, sampling a limited set of loci may not provide enough resolution to accurately resolve a relationship. Instead, whole genome techniques can sample the entirety of the genome or a sufficiently large portion of the genome and as such they may effect better relationship determinations. While relatively common in other areas of study, whole genome techniques have only begun to be explored in the forensic sciences. As such, bioinformatic pipelines are introduced for estimating kinship by massively parallel sequencing of whole genomes using approaches adapted from the medical and population genomic literature. The pipelines are designed to characterize a person’s entire genome, not just some set of targeted markers. Two different variant callers are considered, contrasting a classical variant calling algorithm (BCFtools) to a more modern deep convolution neural network (DeepVariant). Two different bioinformatic pipelines specific to each variant caller are introduced and evaluated in a titration series. Filters and thresholds are then optimized specifically for the purposes of estimating kinship as determined by the KING-robust algorithm. With the appropriate filtering and thresholds in place both tools perform similarly, with DeepVariant tending to produce more accurate genotypes, though the resultant types of inaccuracies tended to produce slightly less accurate overall estimates of relatedness     

Telescoping the origins of obesity to women's bodies: How gender inequalities are being squeezed out of Barker's hypothesis

Aim: This paper traces the genealogy of the Barker hypothesis and its intersections with popular representations of scientific discourses about pregnancy and maternal obesity.

Method: Drawing on Foucault's genealogical method, this study examines the historical ‘descent’ of the developmental origins of adult disease and its initial grounding in structural factors of gender inequality and low socioeconomic status.

Results: In the more recent reproductive medicine literature, Barker's hypothesis has been used to understand the causes and consequences of foetal over-nutrition and has shifted its focus from social determinants to individual, gendered bodies. The print media has gainfully employed this conceptualization of obesity and, in doing so, placed women, and mothers in particular, as causal agents in the reproduction of obesity across generations. Such a ‘common sense’ understanding of obesity production and reproduction means that both the scientific literature and the public understanding of science has inadvertently assisted in putting women forward as the transmitters of obesity across generations.

Conclusions: This powerful telescoping of the origins of obesity to women's bodies and their appetites is in stark contrast to earlier foci on gender inequalities and changing women's circumstances.     

家族性急性髓系白血病差异表达基因的筛选

目的 建立简便可靠的非同位紊杂交筛选方法,筛选家族性急性髓系白血病cDNA消减文库中的差异表达基因.方法 用地高辛(DIG)标记消减文库cDNA作为探针,通过差异筛选技术进行差异表达片段的筛选,杂交阳性结果经RT-PCR再度验证.结果 DIG标记探针浓度为250～500 pg/μL,效率为48%～96%,并且杂交信号清晰,重现性好.应用DIG标记探针改良的差异筛选技术所得到的阳性结果经RT-PCR验证符合率达到86%.结论 采用DIG标记探针具有高度的灵敏度和良好的特异性,可避免放射性污染,简化实验操作,可作为替代同位素32P-dCTP标记探针的方法.     

一对精神分裂症双生子的病证结合研究及背景调查

目的通过41对双生子家系背景的调查积累,探讨双生子研究法引入中西医结合研究的可行性,重点对1对心脾两虚精神分裂症的双生子进行示范性研究。方法按现代遗传学的方法调查积累了41对双生子,鉴定其卵型、家系双生子对数、双生子的出生时间等,并重点进行西医疾病和中医证候诊断,从而筛选到可以进行病证结合研究的9对13个双生子,最后具体分析1对典型单卵双生子。结果获得家系图谱41张,1个家系中2对以上双生子占总调查对数的45%,41对双生子可以病证结合研究的有9对,其中双生子病证相同相近者3对6人。通过对心脾两虚的精神分裂症双生子研究可见,其天然的对称(对照)性,利于复杂证候的动态的时间空间观的分析。结论双生子是遗传与环境相互作用的特殊产物,同病同证的双生子样品具有可比性和可参照性,是研究证候基因组、病因病机、疗效评价的绝好天然模型,是高质量的科学基础材料。     

Differential shuffling of native genetic diversity across introduced regions in a brown alga: aquaculture vs. maritime traffic effects

Worldwide marine invaders, such as the brown alga Undaria pinnatifida, offer challenging models for unraveling the apparent paradox of sustainable settlement of exotic species over a large spectrum of environments. Two intergenic noncoding mitochondrial loci were found to be highly informative at the within-species level. Twenty-five haplotypes were found over the whole dataset (333 base pairs, 524 individuals, and 24 populations). The native range showed striking population genetic structure stemming from low diversity within and high differentiation among populations, a pattern not observed in the introduced range of this seaweed. Contrary to classical expectations of founding effects associated with accidental introduction of exotic species, most of the introduced populations showed high genetic diversity. At the regional scale, genetic diversity and sequence divergence showed contrasting patterns in the two main areas of introduction (Europe and Australasia), suggesting different processes of introduction in the two regions. Gene genealogy analyses point to aquaculture as a major vector of introduction and spread in Europe but implicate maritime traffic in promoting recurrent migration events from the native range to Australasia. The multiplicity of processes and genetic signatures associated with the successful invasion confirms that multiple facets of global change, e.g., aquaculture practices, alteration of habitats, and increased traffic, act in synergy at the worldwide level, facilitating successful pandemic introductions.     

HLA‐A3‐B14 and the origin of the haemochromatosis C282Y mutation: founder effects and recombination events during 12 generations in a Scandinavian family with major iron overload

Background: The haemochromatosis mutation C282Y occurred once in a person who lived in Ireland or Scandinavia and carried either human leucocyte antigen (HLA)‐A3‐B7 or A3‐B14. With time, recombinations are believed to have taken place introducing new HLA haplotypes. This evolution is mainly unknown. In this study, we tried to find a founder, possible recombination events and effect on the phenotype in descendants. Setting: A Swedish mountain population close to Norway, n = 3529, population density <1/km². Methods: Retrospective genealogy study of HLA haplotypes followed by extended haplotype studies. Results: There were 34 probands (22 men, 12 women) where 31 (91%) shared a common founder origin 12 generations ago. The A3‐B14 haplotype was the most common, 39%, in strong linkage disequilibrium (P < 0.0005) with controls, followed by A3‐B7, 20% (P < 0.005), probably resulting from a centromeric recombination replacing the B14 allele with the common B7. Possible telomeric recombinations took place close to HLA‐A and introduced the haplotypes AW19‐B7 (n = 4), AW19‐B27 (2), A1‐B17 (5) and A2‐B12 (4) supported by pedigree studies. Male homozygotes with two copies of HLA‐A3 had significantly (P 0.001) higher mean serum ferritin values than those with one, and liver damage (fibrosis and cirrhosis) was also more common (P < 0.001) than in a population with a recombinant (A1‐B8) haplotype. Conclusions: A3‐B14 may well be the ancestral haplotype with A3B7, the result of centromeric recombinations introducing the common B7 allele. Telomeric recombinations were more common than expected. The ancestral HLA‐A3 haplotype may be associated with a more severe phenotypic expression.