The ratio of de novo unbalanced translocation to 47, trisomy 21 Down syndrome a new method for human mutation surveillance and an apparent recent change in mutation rate resulting in human interchange trisomies in one jurisdiction

1978 ◽  
Vol 52 (3) ◽  
pp. 427-439 ◽  
Author(s):  
Ernest B. Hook
Keyword(s):  
Down Syndrome ◽  
Mutation Rate ◽  
Trisomy 21 ◽  
De Novo ◽  
Recent Change ◽  
New Method ◽  
Unbalanced Translocation ◽  
Human Mutation

De Novo COL7A1 mutation in a patient with trisomy 21: coexistence of dystrophic epidermolysis bullosa and Down syndrome

2012 ◽  
Vol 51 (9) ◽  
pp. 1078-1081
Author(s):  
Javiera A. Catalán ◽  
Fernando A. Rodríguez ◽  
María J. Yubero ◽  
Francis Palisson ◽  
María J. Gana ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Epidermolysis Bullosa ◽  
Trisomy 21 ◽  
De Novo ◽  
Dystrophic Epidermolysis Bullosa

scholarly journals A direct multi-generational estimate of the human mutation rate from autozygous segments seen in thousands of parentally related individuals

2016 ◽  
Author(s):  
Vagheesh M Narasimhan ◽  
Raheleh Rahbari ◽  
Aylwyn Scally ◽  
Arthur Wuster ◽  
Dan Mason ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Base Pair ◽  
De Novo ◽  
Recent Common Ancestor ◽  
Human Populations ◽  
De Novo Mutations ◽  
Pakistani Population ◽  
Human Mutation ◽  
C To T Mutations ◽  
Mutational Processes

AbstractHeterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations (DNMs) across multiple generations. Using exome sequences from 3,222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1. 45 ± 0.05 × 10−8 per base pair per generation in autosomal coding sequence, with a corresponding noncrossover gene conversion rate of 8.75 ± 0.05 × 10−6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent-offspring trios, suggesting that post-zygotic mutations contribute little to the human germline mutation rate. We found frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5’ CCG 3’ → 5’ CTG 3’ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.

Down syndrome with partial trisomy of chromosome 21 because of a de-novo unbalanced translocation t(13;21)(q10;q22)

2012 ◽  
Vol 21 (4) ◽  
pp. 200-203 ◽  
Author(s):  
Emilie Maciejewski ◽  
Jacqueline Vigneron ◽  
Laetitia Lambert ◽  
Céline Bonnet ◽  
Jean-Michel Hascoët
Keyword(s):  
Down Syndrome ◽  
De Novo ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Unbalanced Translocation

scholarly journals Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes

2015 ◽  
Author(s):  
Mark Lipson ◽  
Po-Ru Loh ◽  
Sriram Sankararaman ◽  
Nick Patterson ◽  
Bonnie Berger ◽  
...  
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
Sequence Divergence ◽  
Great Apes ◽  
Human Populations ◽  
De Novo Mutations ◽  
Essential Parameter ◽  
Human Mutation ◽  
Rate Of Accumulation

The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 +/- 0.13 x 10^(-8) mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.

scholarly journals A method to build extended sequence context models of point mutations and indels

2021 ◽  
Author(s):  
Jörn Bethune ◽  
April Kleppe ◽  
Søren Besenbacher
Keyword(s):  
Mutation Rate ◽  
Software Package ◽  
Statistical Power ◽  
De Novo ◽  
Point Mutations ◽  
New Method ◽  
Large Set ◽  
Base Pairs ◽  
Sequence Context ◽  
Strong Constraint

AbstractThe mutation rate of a specific position in the human genome depends on the sequence context surrounding it. Modeling the mutation rate by estimating a rate for each possible k-mer, however, only works for small values of k since the data becomes too sparse for larger values of k. Here we propose a new method that solves this problem by grouping similar k-mers using IUPAC patterns. We refer to the method as k-mer pattern partition and have implemented it in a software package called kmerPaPa. We use a large set of human de novo mutations to show that this new method leads to improved prediction of mutation rates and makes it possible to create models using wider sequence contexts than previous studies. Revealing that for some mutation types, the mutation rate of a position is significantly affected by nucleotides that are up to four base pairs away. As the first method of its kind, it does not only predict rates for point mutations but also indels. We have additionally created a software package called Genovo that, given a k-mer pattern partition model, predicts the expected number of synonymous, missense, and other functional mutation types for each gene. Using this software, we show that the created mutation rate models increase the statistical power to detect genes containing disease-causing variants and to identify genes under strong constraint, e.g. haploinsufficient genes.

Down Syndrome, Other Full Aneuploidies, Polyploidy, and the Influence of Parental Age

2018 ◽  
Author(s):  
R. J McKinlay Gardner ◽  
David J Amor
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
De Novo ◽  
Hydatidiform Mole ◽  
Recurrence Risk ◽  
Chromosome 21 ◽  
Secular Change ◽  
Age Related ◽  
Related Risk ◽  
Chromosome Disorder

This chapter reviews the archetypical chromosome disorder, namely Down syndrome (DS; trisomy 21), and the various different chromosomal forms that may be the basis of it: standard trisomy 21, translocation trisomy, both de novo and inherited, and other rare forms. The concept of dosage imbalance as the basis of the pathogenesis is reviewed, and the “DS critical region” on chromosome 21 is examined. Reproductive risks associated with each of these DS types are discussed. The chapter considers the other full autosomal trisomies, T13 and T18, and also (mosaic) T9. Triploidy, as the basis of hydatidiform mole, is reviewed. Also reviewed are the influence of parental, mostly maternal, age, in the genesis of these aneuploidies, and the effect of secular change on these observations. Tables provide precise age-related risk figures for recurrence risk of T21 and more general figures for other trisomies.

Trisomy 21 q: 46,XX,21s+/47,XX,+21q−(q22→qter) mosaicism (de novo) in a down syndrome child

1984 ◽  
Vol 51 (3) ◽  
pp. 363-366 ◽  
Author(s):  
D. S. Krishna Murthy ◽  
Sabita Roy ◽  
P. M. Contractor ◽  
V. C. Shah
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
De Novo ◽  
Down Syndrome Child ◽  
Syndrome Child

scholarly journals A Rare De Novo Robertsonian Translocation t(21q; 21q) in an Iranian Child With Down Syndrome: A Case Report

2020 ◽  
Author(s):  
Ali Nikfar ◽  
Mojdeh Mansouri ◽  
Gita Fatemi Abhari
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Robertsonian Translocation ◽  
De Novo ◽  
Genetic Disorder ◽  
Female Child ◽  
Medical Sciences ◽  
Nasal Bridge ◽  
Flat Nasal Bridge ◽  
Iranian Child

Down syndrome or trisomy 21 is the most common genetic disorder with a prevalence of 1 in 700 live-born infants. It is characterized by the intellectual disability of varying range, developmental delay, distinctive facial features and various physical abnormalities. The most frequent clinical features include hypotonia, short stature, short neck, upward slanting eyes, flat nasal bridge, bulging tongue, small ears and a single palmar crease of the hands. Mainly there are three cytogenetic forms of Down syndrome including free trisomy 21, mosaicism and Robertsonian translocation. We describe the case of a 1-year-old Iranian female child who presented to our genetic counseling center with intellectual and physical disabilities. The most common features of Down syndrome were present. The cytogenetic analysis confirmed the diagnosis, with detection of the Robertsonian translocation t(21q; 21q). The patient's parents were found to be both phenotypically and cytogenetically normal, so the identified Robertsonian translocation t(21q; 21q) probably have arisen de novo. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(8):522-524.

‘The Stuff of Slow Constitution’: Reading Down Syndrome for Race, Disability, and the Timing that Makes Them So

Somatechnics ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 235-248 ◽  
Author(s):  
Mel Y. Chen
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Historical Perspective ◽  
Early History ◽  
Present Moment ◽  
History Of ◽  
Living Being

In this paper I would like to bring into historical perspective the interrelation of several notions such as race and disability, which at the present moment seem to risk, especially in the fixing language of diversity, being institutionalised as orthogonal in nature to one another rather than co-constitutive. I bring these notions into historical clarity primarily through the early history of what is today known as Down Syndrome or Trisomy 21, but in 1866 was given the name ‘mongoloid idiocy’ by English physician John Langdon Down. In order to examine the complexity of these notions, I explore the idea of ‘slow’ populations in development, the idea of a material(ist) constitution of a living being, the ‘fit’ or aptness of environmental biochemistries broadly construed, and, finally, the germinal interarticulation of race and disability – an ensemble that continues to commutatively enflesh each of these notions in their turn.

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