scholarly journals Founder Effects in Hereditary Hemorrhagic Telangiectasia

2021 ◽  
Vol 10 (8) ◽  
pp. 1682
Author(s):  
Tamás Major ◽  
Réka Gindele ◽  
Gábor Balogh ◽  
Péter Bárdossy ◽  
Zsuzsanna Bereczky
Keyword(s):  
Genetic Algorithms ◽  
Common Core ◽  
Founder Effect ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Founder Mutation ◽  
Founder Effects ◽  
Core Haplotype ◽  
Founder Event ◽  
Mutation Databases ◽  
Smad4 Mutation

A founder effect can result from the establishment of a new population by individuals from a larger population or bottleneck events. Certain alleles may be found at much higher frequencies because of genetic drift immediately after the founder event. We provide a systematic literature review of the sporadically reported founder effects in hereditary hemorrhagic telangiectasia (HHT). All publications from the ACVRL1, ENG and SMAD4 Mutation Databases and publications searched for terms “hereditary hemorrhagic telangiectasia” and “founder” in PubMed and Scopus, respectively, were extracted. Following duplicate removal, 141 publications were searched for the terms “founder” and “founding” and the etymon “ancest”. Finally, 67 publications between 1992 and 2020 were reviewed. Founder effects were graded upon shared area of ancestry/residence, shared core haplotypes, genealogy and prevalence. Twenty-six ACVRL1 and 12 ENG variants with a potential founder effect were identified. The bigger the cluster of families with a founder mutation, the more remarkable is its influence to the populational ACVRL1/ENG ratio, affecting HHT phenotype. Being aware of founder effects might simplify the diagnosis of HHT by establishing local genetic algorithms. Families sharing a common core haplotype might serve as a basis to study potential second-hits in the etiology of HHT.

Juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia associated with a SMAD4 mutation in a girl

2020 ◽  
Vol 13 (6) ◽  
pp. 1096-1101
Author(s):  
Yusuke Hashimoto ◽  
Koji Yokoyama ◽  
Hideki Kumagai ◽  
Yuko Okada ◽  
Takanori Yamagata
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Juvenile Polyposis ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
Smad4 Mutation

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals THE THEORY OF SPECIATION VIA THE FOUNDER PRINCIPLE

Genetics ◽  
1980 ◽  
Vol 94 (4) ◽  
pp. 1011-1038
Author(s):  
Alan R Templeton
Keyword(s):  
Genetic Variability ◽  
Founder Effect ◽  
Ancestral Population ◽  
Founder Population ◽  
Hawaiian Drosophila ◽  
Severe Reduction ◽  
Selective Forces ◽  
Theoretical Population ◽  
Adaptive Peak ◽  
Founder Event

ABSTRACT The founder principle has been used to explain many instances of rapid speciation. Advances from theoretical population genetics are incorporated into MAYR'S original founder-effect genetic-revolution model to yield a newer model called the genetic transilience. The basic theoretical edifice lies upon the fact that founder event can sometimes lead to an accumulation of inbreeding and an induction of gametic disequilibrium. This, in turn, causes alleles to be selected more for their homozygous fitness effects and for their effects on a more stable genetic background. Selection occurring in multi-locus systems controlling integrated developmental, physiological, behavioral, etc., traits is particularly sensitive to these founder effects. If sufficient genetic variability exists in the founder population, such multilocus genetic systems can respond to drift and the altered selective forces by undergoing a rapid shift to a new adaptive peak known as the genetic transilience. A genetic transilience is, therefore, most likely to occur when the founder event causes a rapid accumulation of inbreeding without a severe reduction in genetic variability. The implications of this model are then examined for three aspects of the founder-effect genetic-transilience model: the attributes of the ancestral population, the nature of the sampling process used t o generate the founders and the attributes of the founder population. The model is used to explain several features of the evolution of the Hawaiian Drosophila, and experimental designs are outlined to test the major predictions of the theory. Hence, this theory of speciation can be tested in the laboratory, using systems and techniques that already exist—a rare attribute of most models of speciation.

Genetic adaptation and founder effect in laboratory populations of the entomopathogenic nematode Steinernema glaseri

1996 ◽  
Vol 74 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Robin J. Stuart ◽  
Randy Gaugler
Keyword(s):  
Founder Effect ◽  
Galleria Mellonella ◽  
Entomopathogenic Nematode ◽  
Reproductive Potential ◽  
Laboratory Culture ◽  
Popillia Japonica ◽  
Founder Effects ◽  
Japanese Beetle ◽  
Laboratory Adaptation ◽  
Steinernema Glaseri

Laboratory culture can have detrimental effects on populations through adverse environmental conditions such as poor nutrition or disease, or through genetic effects such as inbreeding depression, founder effect, genetic drift, or laboratory adaptation. We tested for laboratory effects on the entomopathogenic nematode Steinernema glaseri (Steiner) by forming a genetically diverse base population from a series of field isolates and rearing several independent lines through 12 cycles of laboratory culture, using larvae of the greater wax moth, Galleria mellonella (L.), or the Japanese beetle, Popillia japonica Newman, as hosts. Laboratory bioassays based on G. mellonella indicated that lines maintained with large breeding populations did not deteriorate but often showed significant increases in infectivity (15.3–48.0%), proportion of males (12.2–36.1%), and reproductive potential (39.0–160.4%). Lines reared on P. japonica larvae responded similarly to lines reared on G. mellonella but showed higher levels of reproductive potential. Two of three lines subjected to initial genetic bottlenecks to test for founder effects differed from other lines by showing very high infectivity but little change in sex ratio or reproductive potential. These results demonstrate that laboratory adaptation can produce dramatic changes in important biological attributes of these nematodes, but that a lack of genetic variation associated with founder effects can impede this process. Laboratory adaptation should be considered a potent factor when designing, interpreting, and comparing studies of this important group of biological control organisms.

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9255 ◽  
Author(s):  
Carlos Farkas ◽  
Francisco Fuentes-Villalobos ◽  
Jose Luis Garrido ◽  
Jody Haigh ◽  
María Inés Barría
Keyword(s):  
Next Generation Sequencing ◽  
North America ◽  
Founder Mutation ◽  
Point Mutations ◽  
Founder Effects ◽  
Sequence Read Archive ◽  
Geographical Regions ◽  
Viral Testing ◽  
Primer Sets ◽  
Generation Sequencing

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

SMAD4 Mutation and Combined Juvenile Polyposis Syndrome/Hereditary Hemorrhagic Telangiectasia

2018 ◽  
Vol 113 (Supplement) ◽  
pp. S850
Author(s):  
Jack Scolaro ◽  
Deena Kapadia ◽  
Houssam Kharrat ◽  
Vani Thirumala ◽  
Seshadri Thirumala
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Juvenile Polyposis ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
Smad4 Mutation

scholarly journals Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Li ◽  
Sile Han ◽  
Cuiyun Zhang ◽  
Yanlin Luo ◽  
Li Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Founder Effect ◽  
Haplotype Analysis ◽  
Founder Mutation ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Target Sequencing ◽  
Recurrent Mutations ◽  
Different Populations

Predisposition of germline BRCA1/2 mutations (gBRCAMUT) increases the risk of breast and ovarian cancer in females, but the mutation prevalence and spectrum are highly ethnicity-specific with different recurrent mutations being reported in different populations. Hereby, we performed hybridization-based target sequencing of BRCA1/2 in 530 ovarian cancer patients from Henan, the central region of China, followed by haplotype analysis of six short tandem repeat (STR) markers in the patients with recurrent mutations to determine their founder effect. About 28.3% (150/530) of the OC patients in our cohort harbored gBRCAMUT; of the 151 mutations, 117 in BRCA1 and 34 in BRCA2, identified in this study, BRCA1:c.5470_5477del, c.981_982del, and c.4065_4068del are the top three mutants, recurrently detected in eight, seven, and six independent patients respectively. Haplotype analysis identified a region of 0.6 MB genomic length covering BRCA1 highly conserved across all eight carriers of BRCA1:c.5470_5477del, but not c.981_982del, suggesting a consequence of founder effect. Retrospective analysis in a subgroup of serous ovarian cancer patients revealed gBRCAMUT status was not associated with the progression-free survival (PFS); instead, an expression of Ki-67% ≥50% was associated with a shorter PFS (p = 0.041). In conclusion, patients with pathogenic or likely pathogenic gBRCAMUT account for 28.3% of the OC cases from Henan, and BRCA1:c.5470_5477del, the most frequently detected mutation in Henan patients, is a founder mutation in the population.

scholarly journals Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

2020 ◽  
Author(s):  
Carlos Farkas ◽  
Francisco Fuentes-Villalobos ◽  
José Luis Garrido ◽  
Jody J Haigh ◽  
María Inés Barría
Keyword(s):  
Founder Mutation ◽  
Point Mutations ◽  
Washington Dc ◽  
Founder Effects ◽  
High Quality ◽  
Coding Regions ◽  
Sequence Read Archive ◽  
Geographical Regions ◽  
Viral Testing ◽  
Primer Sets

AbstractHere we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

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