scholarly journals Сytogenetic techniques in current biomedical research. part i: history and theoretical basis of human cytogenetics

2021 ◽  
Vol 6 (4) ◽  
pp. 142-150
Author(s):  
A. N. Volkov ◽  
L. V. Nacheva
Keyword(s):  
Molecular Basis ◽  
Human Genetics ◽  
Chromosomal Abnormalities ◽  
Unmet Need ◽  
Genetic Load ◽  
Reproductive Function ◽  
Human Populations ◽  
Chromosomal Structure ◽  
Social Burden ◽  
Human Cytogenetics

Cytogenetics is an essential part of human genetics which studies the structure of chromosomes and their collection which is called karyotype. Cytogenetic techniques are employed while interrogating DNA organisation and compaction. Analysis of the chromosomal structure contributes to uncovering the molecular basis of various cellular processes in normal and pathological conditions. Furthermore, spectrum and frequency of chromosome abnormalities serves as an indicator of mutagenic effects. Cytogenetic techniques became indispensable for discovering the genetic causes of human diseases at different stages of ontogenesis. Genetic abnormalities are a common cause of impaired reproductive function, abnormal pregnancy, and neonatal malformations. Genetic screening for chromosomal abnormalities and congenital anomalies is a powerful tool for reducing the genetic load in human populations as well as disease, psychological and social burden on families and societies. This paper begins the cycle of lectures on molecular basis of human cytogenetics, cytogenetic techniques, and the corresponding research and clinical applications. The lecture is primarily aimed at biomedical students and physicians who often have an unmet need to analyse and interpret the results of cytogenetic analyses.

scholarly journals Dynamics of natural selection in two generations (on the example of the population of the Kirovograd region)

2021 ◽  
Vol 29 ◽  
pp. 152-156
Author(s):  
K. K. Kovleva ◽  
N.A. Kozak
Keyword(s):  
Natural Selection ◽  
First Generation ◽  
Second Generation ◽  
Selection Index ◽  
Genetic Load ◽  
Modern Medicine ◽  
Reproductive Age ◽  
Human Populations ◽  
Medical Histories ◽  
Total Selection

Aim. In connection with the success of modern medicine, the pressure of natural selection in various civilized human populations is weakening, which leads to the accumulation of a genetic load. The purpose of this work was to trace the change in the intensity of natural selection among population of the Kirovograd region in two successive generations. Methods. The collection of material was carried out in 2020 and 2021. Anonymous questionnaires were conducted and medical histories of women of post-reproductive age of the Kirovograd region were studied. The first generation included 40 women born in 1937–1959; the second generation consists of 273 women born in 1960–1981. Results. The total selection index was 0.27 in the first generation, and 0.37 in the second generation. The percentage of women who have not had pregnancies increased from the first generation to the second from 2.5 to 3.7, respectively. Conclusions. The index of total selection in the Kirovograd region population for one generation increased by almost one and a half times (from 0.27 to 0.37), as well as the index of differential fertility (from 0.25 to 0.35). Keywords: reproductive characteristics, Kirovograd population, Crow's index, selection, generations.

scholarly journals svtools: population-scale analysis of structural variation

2019 ◽  
Vol 35 (22) ◽  
pp. 4782-4787 ◽  
Author(s):  
David E Larson ◽  
Haley J Abel ◽  
Colby Chiang ◽  
Abhijit Badve ◽  
Indraniel Das ◽  
...  
Keyword(s):  
Large Scale ◽  
Structural Variation ◽  
Human Genetics ◽  
Mobile Element ◽  
Supplementary Information ◽  
Joint Analysis ◽  
Human Populations ◽  
Scale Analysis ◽  
Human Genomes ◽  
Variant Detection

Abstract Summary Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps—including deletions, duplications, mobile element insertions, inversions and other rearrangements—in many thousands of human genomes. We show that this pipeline achieves similar variant detection performance to established per-sample methods (e.g. LUMPY), while providing fast and affordable joint analysis at the scale of ≥100 000 genomes. These tools will help enable the next generation of human genetics studies. Availability and implementation svtools is implemented in Python and freely available (MIT) from https://github.com/hall-lab/svtools. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans

2017 ◽  
Author(s):  
Matthias Steinrücken ◽  
Jeffrey P. Spence ◽  
John A. Kamm ◽  
Emilia Wieczorek ◽  
Yun S. Song
Keyword(s):  
Genetic Material ◽  
Genetic Load ◽  
Modern Human ◽  
Human Populations ◽  
Effective Population ◽  
Weak Selection ◽  
Modern Humans ◽  
High Coverage ◽  
Model Based ◽  
And Migration

AbstractGenetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair- and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method called diCal-admix and apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.

scholarly journals “Genetic Load”: How the Architects of the Modern Synthesis Became Trapped in a Scientific Ideology

2018 ◽  
pp. 118
Author(s):  
Alexandra Soulier
Keyword(s):  
Theoretical Basis ◽  
Policy Making ◽  
Natural Populations ◽  
Genetic Load ◽  
Social Progress ◽  
Human Populations ◽  
Complex Phenomenon ◽  
Science And Policy ◽  
Theodosius Dobzhansky ◽  
Combined Actions

The term “genetic load” first emerged in a paper written in 1950 by the geneticist H. Muller. It is a mathematical model based on biological, social, political and ethical arguments describing the dramatic accumulation of disadvantageous mutations in human populations that will occur in modern societies if eugenic measures are not taken. The model describes how the combined actions of medical and social progress will supposedly impede natural selection and make genes of inferior quality likely to spread across populations – a process which in fine loads their progress. Genetic load is based on optimal fitness and emerges from a “typological view” of evolution. This model of evolution had previously, however, been invalidated by Robert Wright and Theodosius Dobzhansky who, as early as 1946, showed that polymorphism was the rule in natural populations. The blooming and persistence of the concept of genetic load, after its theoretical basis had already expired, are a historical puzzle. This persistence reveals the intricacy of science and policy-making in eugenic matters. The Canguilhemian concept of ‘scientific ideology’ (1988) is used along with the concept of ‘immutable mobile’ (Latour 1986) and compared with the concept of ‘co-production’ (Jasanoff 1998), to provide complementary perspectives on this complex phenomenon.

scholarly journals Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load

2021 ◽  
Author(s):  
Beatriz Navarro-Dominguez ◽  
Ching-Ho Chang ◽  
Cara Brand ◽  
Christina Muirhead ◽  
Daven Presgraves ◽  
...  
Keyword(s):  
Genetic Load ◽  
Meiotic Drive ◽  
Fruit Fly ◽  
Common Mechanism ◽  
Mendelian Segregation ◽  
Chromosomal Structure ◽  
Synonymous Mutations ◽  
Segregation Distorter ◽  
History Of ◽  
Chromosome Variant

Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation to gain preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing alternative alleles. While at least two loci are important for male drive- the driver and the target- linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversion on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over and with wildtype chromosomes only via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.

A new paradigm in CLL: Minimizing toxicity by using the minimum effective dose (MED) of lenalidomide for older patients with CLL.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6609-6609
Author(s):  
Nicole Lamanna ◽  
Mark L. Heaney ◽  
Peter George Maslak ◽  
Joseph G. Jurcic ◽  
Todd L. Rosenblat ◽  
...  
Keyword(s):  
Disease Control ◽  
Older Patients ◽  
Low Dose ◽  
Chromosomal Abnormalities ◽  
Unmet Need ◽  
Continuous Treatment ◽  
Hematologic Toxicity ◽  
New Paradigm ◽  
Prior Therapy

6609 Background: While CIT has proven active for younger patients with CLL; studies from Germany and MDACC with fludarabine or fludarabine- based regimens did not benefit the patient over the age of 65 or 70. As the median age of diagnosis is 72, the development of safe, active therapies for older patients is an unmet need in CLL. Lenalidomide is an active drug in CLL. The current clinical trial was designed to assess whether low-dose continuous lenalidomide therapy can provide long-term disease control with minimum toxicity in patients older than 65. Methods: Patients initiate lenalidomide at 2.5mg daily (28-day cycle) and only dose escalate for progressive disease (POD). Results: 18 patients have been enrolled: 12 men and 6 women, med age 70 (range 65-84) with Rai-intermediate (7 pts) or high-risk (11 pts; 61%) disease; med WBC 50.5 (6.7-326.3), HGB 10.3 (8.9-13.9), PLT 121 (44-215), β-2 microglobulin 4.9 (3.0-10.2). 16 (89%) patients had chromosomal abnormalities: 3 with 13q, 6 with tris 12, 3 with 11q, and 4 with 17p. 13 (72%) patients have unmutated IGHV. 5 (28%) patients were previously untreated; 13 (72%) had prior therapy (range 1-5; med 2). Median dose of lenalidomide is 2.5mg (range 2.5mg-10mg); median no. cycles is 7 (range 1-28). 11 patients (61%) are still on therapy (7 previously treated): 6 at 2.5mg; 4 at 5mg, and 1 at 10mg. 7 have discontinued therapy: 1 for ITP; 3 for POD including one with Richter’s, 2 for desquamating rash; and 1 withdrew consent. Only 2 patients had tumor lysis and 10 had tumor flare (8 given steroids briefly). In these older patients on long-term continuous treatment, therapy has been generally well tolerated. There have been no deaths on study. Pneumonia developed in 4 patients (3 of these had prior therapy). 1 patient with history of atrial fibrillation developed DVT/PE. Main hematologic toxicity is neutropenia seen in 11 patients but transient. Grade 3/4 thrombocytopenia and anemia was seen in 5 and 0 patients, respectively. Conclusions: Low-dose continuous lenalidomide therapy iappears to be well-tolerated and may offer long term disease control in some patients with CLL. Additional accrual and longer follow-up will be required to further assess the utility of this strategy.

scholarly journals Molecular Basis of Slo Channel(S) Function in Sperm Revealed by Human Genetics

2015 ◽  
Vol 108 (2) ◽  
pp. 280a
Author(s):  
Steven A. Mansell ◽  
Sarah Martins da Silva ◽  
Melissa Miller ◽  
Christopher L.R. Barratt ◽  
Polina V. Lishko
Keyword(s):  
Molecular Basis ◽  
Human Genetics

Flattening and Unpacking Human Genetic Variation in Mexico, Postwar to Present

2017 ◽  
Vol 30 (1) ◽  
pp. 89-112 ◽  
Author(s):  
Víctor Hugo Anaya-Muñoz ◽  
Vivette García-Deister ◽  
Edna Suárez-Díaz
Keyword(s):  
Genetic Variation ◽  
Native American ◽  
Human Genetics ◽  
Genomic Diversity ◽  
Human Populations ◽  
Research Strategies ◽  
Fine Grained ◽  
Multidisciplinary Analysis ◽  
The 1960S ◽  
Social Demographic

ArgumentThis paper analyzes the research strategies of three different cases in the study of human genetics in Mexico – the work of Rubén Lisker in the 1960s, INMEGEN's mapping of Mexican genomic diversity between 2004 and 2009, and the analysis of Native American variation by Andrés Moreno and his colleagues in contemporary research. We make a distinction between an approach that incorporates multiple disciplinary resources into sampling design and interpretation (unpacking), from one that privileges pragmatic considerations over more robust multidisciplinary analysis (flattening). These choices have consequences for social, demographic, and biomedical practices, and also for accounts of genetic variation in human populations. While the former strategyunpacksfine-grained genetic variation – favoring precision and realism, the latter tends toflattenindividual differences and historical depth in lieu of generalization.

The molecular basis and reproductive function(s) of copulatory plugs

2016 ◽  
Vol 83 (9) ◽  
pp. 755-767 ◽  
Author(s):  
Marlon R. Schneider ◽  
Rachel Mangels ◽  
Matthew D. Dean
Keyword(s):  
Molecular Basis ◽  
Reproductive Function ◽  
Copulatory Plugs
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