scholarly journals Should results of HLA haplotype frequency estimations be normalized?

2021 ◽  
Author(s):  
Susanne Seitz ◽  
Vinzenz Lange ◽  
Paul J. Norman ◽  
Jürgen Sauter ◽  
Alexander H. Schmidt
Keyword(s):  
Haplotype Frequency

scholarly journals A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Keith A. Josephs ◽  
Joseph R. Duffy ◽  
Heather M. Clark ◽  
Rene L. Utianski ◽  
Edythe A. Strand ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Molecular Pathology ◽  
Age At Onset ◽  
Haplotype Frequency ◽  
Corticobasal Degeneration ◽  
Apraxia Of Speech ◽  
Speech Characteristics ◽  
Biochemical Genetic ◽  
Neuroimaging Study ◽  
Longitudinal Imaging

AbstractProgressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.

scholarly journals Association between EFHD2 gene polymorphisms and schizophrenia among the Han population in northern China

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093280
Author(s):  
Meng Gao ◽  
Kuo Zeng ◽  
Ya Li ◽  
Yong-ping Liu ◽  
Xi Xia ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Neurodevelopmental Disorder ◽  
Haplotype Frequency ◽  
Northern China ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Gene Encoding ◽  
Frequency Distributions ◽  
And Control

Objective Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. The gene encoding EF-hand domain-containing protein D2 ( EFHD2) may be a genetic risk locus for schizophrenia. Methods We genotyped four EFHD2 single-nucleotide polymorphisms (281 schizophrenia cases [SCZ], 321 controls) from northern Chinese Han individuals using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Differences existed in genotype, allele, and haplotype frequency distributions between SCZ and control groups. Results The rs2473357 genotype and allele frequency distributions differed between SCZ and controls; however, this difference disappeared after Bonferroni correction. Differences in rs2473357 genotype and allele frequency distributions between SCZ and controls were more pronounced in men than in women. The G allele increased schizophrenia risk (odds ratio = 1.807, 95% confidence interval = 1.164–2.803). Among six haplotypes (G–, A–, G-insC, A-C, G-C, and G-T), the G– haplotype frequency distribution differed between SCZ and controls in women; the A-C and G-C haplotype frequency distributions differed between SCZ and controls in men. Conclusions EFHD2 may be involved in schizophrenia. Sex differences in EFHD2 genotype and allele frequency distributions existed among schizophrenia patients. Further research is needed to determine the role of EFHD2 in schizophrenia.

scholarly journals X-chromosomal STR based genetic polymorphisms and demographic history of Sri Lankan ethnicities and their relationship with global populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nandika Perera ◽  
Gayani Galhena ◽  
Gaya Ranawaka
Keyword(s):  
Allele Frequency ◽  
Demographic History ◽  
Evolutionary Genetics ◽  
Haplotype Frequency ◽  
Allele Frequency Distribution ◽  
Sri Lankan ◽  
Frequency Distributions ◽  
Autosomal Str ◽  
History Of ◽  
Multiplex System

AbstractA new 16 X-short tandem repeat (STR) multiplex PCR system has recently been developed for Sr Lankans, though its applicability in evolutionary genetics and forensic investigations has not been thoroughly assessed. In this study, 838 unrelated individuals covering all four major ethnic groups (Sinhalese, Sri Lankan Tamils, Indian Tamils and Moors) in Sri Lanka were successfully genotyped using this new multiplex system. The results indicated a high forensic efficiency for the tested loci in all four ethnicities confirming its suitability for forensic applications of Sri Lankans. Allele frequency distribution of Indian Tamils showed subtle but statistically significant differences from those of Sinhalese and Moors, in contrast to frequency distributions previously reported for autosomal STR alleles. This suggest a sex biased demographic history among Sri Lankans requiring a separate X-STR allele frequency database for Indian Tamils. Substantial differences observed in the patterns of LD among the four groups demand the use of a separate haplotype frequency databases for each individual ethnicity. When analysed together with other 14 world populations, all Sri Lankan ethnicities except Indian Tamils clustered closely with populations from Indian Bhil tribe, Bangladesh and Europe reflecting their shared Indo-Aryan ancestry.

scholarly journals Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching

2021 ◽  
Vol 17 (7) ◽  
pp. e1009248
Author(s):  
Matthias Niemann ◽  
Nils Lachmann ◽  
Kirsten Geneugelijk ◽  
Eric Spierings
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
Haplotype Frequency ◽  
Deceased Donor ◽  
Waiting List ◽  
T Cell Epitopes ◽  
Kidney Allocation ◽  
Virtual Population ◽  
Considerable Impact ◽  
The Impact

The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We here executed ETKAS-based computer simulations to evaluate the impact of epitope matching on allocation and compared the strategies. A virtual population of 400,000 individuals was generated using the National Marrow Donor Program (NMDP) haplotype frequency dataset of 2011. Using this population, a waiting list of 10,400 patients was constructed and maintained during simulation, matching the 2015 Eurotransplant Annual Report characteristics. Unacceptable antigens were assigned randomly relative to their frequency using HLAMatchmaker. Over 22,600 kidneys were allocated in 10 years in triplicate using Markov Chain Monte Carlo simulations on 32-CPU-core cloud-computing instances. T-cell epitopes were calculated using the www.pirche.com portal. Waiting list effects were evaluated against ETKAS for five epitope matching scenarios. Baseline simulations of ETKAS slightly overestimated reported average HLA match grades. The best balanced scenario maintained prioritisation of HLA A-B-DR fully matched donors while replacing the HLA match grade by PIRCHE-II score and exchanging the HLA mismatch probability (MMP) by epitope MMP. This setup showed no considerable impact on kidney exchange rates and waiting time. PIRCHE-II scores improved, whereas the average HLA match grade diminishes slightly, yet leading to an improved estimated graft survival. We conclude that epitope-based matching in deceased donor kidney allocation is feasible while maintaining equal balances on the waiting list.

scholarly journals Forensic application of Y-chromosomal STR analysis in Lithuanian population

Biologija ◽  
2015 ◽  
Vol 61 (2) ◽  
Author(s):  
Giedrė Ruzgaitė ◽  
Marija Čaplinskienė ◽  
Rima Baranovienė ◽  
Jūratė Jankauskienė ◽  
Jolanta Kukienė ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Gene Pool ◽  
Haplotype Diversity ◽  
Haplotype Frequency ◽  
Reference Database ◽  
Match Probability ◽  
Str Analysis ◽  
Str Markers ◽  
Forensic Casework ◽  
Chromosome Gene

This paper presents a comprehensive Y-chromosomal STR haplotype analysis in the Lithuanian population in order to evaluate Lithuanians’ Y chromosome diversity, to infer genetic relations between Lithuanian and other European neighbouring populations and to introduce population reference data for generation of reliable Y-STR haplotype frequency estimates to be used in the quantitative assessment of Y-STR haplotype match in the forensic casework. Data were collected from the peripheral blood samples of 194 unrelated males throughout various regions of Lithuania. The amplification of 17 Y-STRs was carried out in one multiplex PCR using an  AmpFlSTR® Yfiler<sup>TM</sup> PCR Amplication Kit according to the supplier’s protocol. The results indicated that the Y-chromosomal haplotype diversity in the Lithuanian population rises as the  number of the  analyzed Y-STRs is increased. However, all additional Y-STR loci are not hypervariable and only their whole makes a large diversity of Y-STR haplotypes in Lithuanian males. The  analysis of molecular variance revealed low but significant interpopulation differences except the pair of Lithuanian and Latvian populations. The  phylogenetic analysis showed that the  clustered Y chromosome gene pool of Lithuanians and Latvians has a closer phylogenetic relation to Russian and Estonian populations and is less genetically related to other neighbouring populations of Belarus and Poland. Yet Y-STRs alleles and haplotypes differentiate effectively inside the  Lithuanian population and between Lithuanians and its geographical neighbours excluding the  Latvian population. Comparison of the Y-STR data suggests that Lithuanian and Latvian populations are closely related not only by geography and language but also by the Y chromosome gene pool represented by forensic Y-STR markers. Consequently, more forensic Y-STR markers should be included in the Y-STR haplotype in order to achieve a resolution between the  Y chromosomes of Lithuanian and Latvian males. Lithuanian Y-STR haplotype data were submitted to the 34th release of the Y-STR Haplotype Reference Database 3.0 for match probability calculations in the forensic casework.

scholarly journals Bone marrow donor registries: the relation between registry size and probability of finding complete and partial matches [see comments]

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2569-2578 ◽  
Author(s):  
FA Sonnenberg ◽  
MH Eckman ◽  
SG Pauker
Keyword(s):  
Bone Marrow ◽  
Human Leukocyte ◽  
Haplotype Frequency ◽  
Cost Effective ◽  
Frequency Data ◽  
Maximum Probability ◽  
Donor Pool ◽  
Leukocyte Antigen ◽  
Middle Range

Abstract In a registry of volunteer bone marrow donors, the relation between registry size and probability of finding an exact or partial match for a random recipient cannot be theoretically derived because it depends on specifics of the human leukocyte antigen (HLA) haplotype frequencies in the donor and recipient populations. The relation must be explicitly calculated using empirically determined HLA haplotype frequency data for all possible pairings between a donor and a recipient population. This report describes a general solution to this problem. The method shows that the relation of the probability of matching to registry size is sigmoidal, with small increases in probability at the extremes of registry size and a middle range of registry size within which the probability of matching increases most sharply. This range determines the approximate size of the most cost-effective registry. In addition, for any pairing of donor and recipient populations, there is a maximum probability of identifying a match of a given quality for a random recipient, which cannot be exceeded even if registry size were infinite. This upper limit is a function of the frequency of blank (or unknown) alleles in the donor and recipient populations; the higher that frequency, the lower the maximum probability of achieving any given quality of match. The determinants of the probability of achieving a given quality of match with a given registry size are (1) the genetic heterogeneity within the recipient and donor populations, which increases the registry size required to achieve a given probability of matching, and (2) the degree of genetic homology between the donor and recipient populations, which increases the maximum probability of matching and also lowers registry size requirements. The method described here can be used to estimate donor pool size requirements using any donor and recipient populations for which HLA frequency data are available.

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