Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'Drift mapping' in small populations with no demographic expansion

Linkage disequilibrium has been a powerful tool in identifying rare disease alleles in human populations. To date, most research has been directed to isolated populations which have undergone a bottleneck followed by rapid exponential expansion. While this strategy works well for rare diseases in which all disease alleles in the population today are clonal copies of some common ancestral allele, for common disease genes with substantial allelic heterogeneity, this approach is not predicted to work. In this paper, we describe the dynamics of linkage disequilibrium in populations which have not undergone a demographic expansion. In these populations, it is shown that genetic drift creates disequilibrium over time, while in expanded populations, the disequilibrium decays with time. We propose that common disease alleles might be more efficiently identified by drift mapping - linkage disequilibrium mapping in small, old populations of constant size where the disequilibrium is the result of genetic drift, not founder effect. Theoretical models, empirical data, and simulated population models are presented as evidence for the utility of this approach

The date of interbreeding between Neandertals and modern humans

Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000-65,000 years ago. This supports the recent interbreeding hypothesis, and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa

Demographic history and genetic differentiation in apes

SummaryComparisons of genetic variation between humans and great apes are hampered by the fact that we still know little about the demographics and evolutionary history of the latter species [1–4]. In addition, characterizing ape genetic variation is important because they are threatened with extinction, and knowledge about genetic differentiation among groups may guide conservation efforts [5]. We sequenced multiple intergenic autosomal regions totaling 22,400 base pairs (bp) in ten individuals each from western, central, and eastern chimpanzee groups and in nine bonobos, and 16,000 bp in ten Bornean and six Sumatran orangutans. These regions are analyzed together with homologous information from three human populations and gorillas. We find that whereas orangutans have the highest diversity, western chimpanzees have the lowest, and that the demographic histories of most groups differ drastically. Special attention should therefore be paid to sampling strategies and the statistics chosen when comparing levels of variation within and among groups. Finally, we find that the extent of genetic differentiation among “subspecies” of chimpanzees and orangutans is comparable to that seen among human populations, calling the validity of the “subspecies” concept in apes into question

Disability discourse, physiotherapy and physical activity in the lives of people with traumatic spinal cord injury

The aim of this study was to explore the experiences with disability discourse, physiotherapy and physical activity (PA) of people with traumatic spinal cord injury (SCI). Eight men with traumatic SCI participated in the study. Semi-structured interviews were carried out with each participant. The participants emphasized the importance of peer counselling in coping with traumatic SCI but also identified several problems in their everyday lives: limited outside mobility during the winter months, limited accessibility, different disturbing societal attitudes and behaviours towards people using a wheelchair, and limited financial aid for people with disabilities. They had mostly positive experiences with physiotherapy and suggested that physiotherapists should focus on developing their general competencies and using an individual client-centred approach. The participants valued PA but were rather inactive due to function- and health-related, motivational and socio-environmental barriers. The combination of different barriers and facilitators to PA varied for each participant, thereby demonstrating the heterogeneity of their PA experiences. When looking at the described benefits of both physiotherapy and PA, the main forms of creating a strong sense of self-efficacy were represented

Simultaneous precise editing of multiple genes in human cells

Abstract. When double-strand breaks are introduced in a genome by CRISPR they are repaired either by non-homologous end joining (NHEJ), which often results i

Taastusravi- ja rehabilitatsioonisüsteemi korraldus

Eesti Arst 2022; 101(1):7–1

Functional analyses of transcription factor binding sites that differ between present-day and archaic humans

We analyze 25 previously identified transcription factor binding sites that carry DNA sequence changes that are present in all or nearly all present-day humans, yet occur in the ancestral state in Neandertals and Denisovans, the closest evolutionary relatives of humans. When the ancestral and derived forms of the transcription factor binding sites are tested using reporter constructs in 3 neuronal cell lines, the activity of 12 of the derived versions of transcription factor binding sites differ from the respective ancestral variants. This suggests that the majority of this class of evolutionary differences between modern humans and Neandertals may affect gene expression in at least some tissue or cell type