Silver–Russell syndrome caused by trisomy 11p15.5 due to a derivative X chromosome from a de novo t(X;11) in a Mexican female patient

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with ade novoX;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed ade novobalanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated withde novobalanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

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Chromosome-level assembly of Drosophila bifasciata reveals important karyotypic transition of the X chromosome

10.1101/847558 ◽

2019 ◽

Author(s):

Ryan Bracewell ◽

Anita Tran ◽

Kamalakar Chatla ◽

Doris Bachtrog

Keyword(s):

X Chromosome ◽

Genome Assembly ◽

De Novo ◽

Pericentromeric Region ◽

Species Group ◽

Chromosome 15 ◽

Protein Coding ◽

Protein Coding Genes ◽

Long Read ◽

Chromosome Level

ABSTRACTThe Drosophila obscura species group is one of the most studied clades of Drosophila and harbors multiple distinct karyotypes. Here we present a de novo genome assembly and annotation of D. bifasciata, a species which represents an important subgroup for which no high-quality chromosome-level genome assembly currently exists. We combined long-read sequencing (Nanopore) and Hi-C scaffolding to achieve a highly contiguous genome assembly approximately 193Mb in size, with repetitive elements constituting 30.1% of the total length. Drosophila bifasciata harbors four large metacentric chromosomes and the small dot, and our assembly contains each chromosome in a single scaffold, including the highly repetitive pericentromere, which were largely composed of Jockey and Gypsy transposable elements. We annotated a total of 12,821 protein-coding genes and comparisons of synteny with D. athabasca orthologs show that the large metacentric pericentromeric regions of multiple chromosomes are conserved between these species. Importantly, Muller A (X chromosome) was found to be metacentric in D. bifasciata and the pericentromeric region appears homologous to the pericentromeric region of the fused Muller A-AD (XL and XR) of pseudoobscura/affinis subgroup species. Our finding suggests a metacentric ancestral X fused to a telocentric Muller D and created the large neo-X (Muller A-AD) chromosome ∼15 MYA. We also confirm the fusion of Muller C and D in D. bifasciata and show that it likely involved a centromere-centromere fusion.

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Role of De Novo DNA Methyltransferases in Initiation of Genomic Imprinting and X-Chromosome Inactivation

Cold Spring Harbor Symposia on Quantitative Biology ◽

10.1101/sqb.2004.69.125 ◽

2004 ◽

Vol 69 (0) ◽

pp. 125-130 ◽

Cited By ~ 19

Author(s):

M. KANEDA ◽

T. SADO ◽

K. HATA ◽

M. OKANO ◽

N. TSUJIMOTO ◽

...

Keyword(s):

Genomic Imprinting ◽

X Chromosome ◽

De Novo ◽

Dna Methyltransferases ◽

X Chromosome Inactivation ◽

Chromosome Inactivation

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THE ORIGIN OF THE MUTATION IN FAMILIES WITH AN ISOLATED CASE OF HAEMOPHILIA A

10.1055/s-0038-1644015 ◽

1987 ◽

Cited By ~ 1

Author(s):

A H J T Bröcker-Vriends ◽

E Briët ◽

J C F M Dreesen ◽

E Bakker ◽

J J P van de Kamp ◽

...

Keyword(s):

X Chromosome ◽

High Probability ◽

Dna Analysis ◽

De Novo ◽

Dna Fingerprint ◽

De Novo Mutation ◽

Clotting Factor ◽

Mutational Event ◽

Haemophilia A ◽

Maternal Grandfather

Approximately one third of the patients with haemophilia appears to have no affected relatives. The proportion of cases due to a new mutational event as well as the gamete origin of the mutation has been much debated. The objective of this study was to define the origin of the mutation in families with an isolated case by DNA analysis. We investigated 22 families with an isolated case of haemophilia A. Intragenic (Bell, Xbal) and extragenic (BglII/DX13, Taql/Stl4) RFLPs were investigated for. If necessary, paternity was tested by DNA fingerprint patterns obtained with the 33.15 mini satellite probe.In seven of the 22 families it could be demonstratedthat the abnormal X-chromosome of the haemophiliac was derived from the normal maternal grandfather. In six of these 7 families the mother of the patient had a high probability of carriershio on the basis of clotting factor VIII assays, so that, probably, the mutation had occurred in the paternal gamete. As a consequence, carriership could be excluded for aunts, nieces and more distant female relatives of the patient.In three families the abnormal X-chromosome was derived from the maternal grandmother, while, sofar, in the remaining 12 families no conclusions as to the origin of the mutation could be drawn.In contrast with earlier findings, these results illustrate that at least thirty percent of the isolatedcases of haemophilia A are due to a recent de novo mutation.

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De Novo Mutation of Paternal IGF2 Gene Causing Silver–Russell Syndrome in a Sporadic Patient

Frontiers in Genetics ◽

10.3389/fgene.2017.00105 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 17

Author(s):

Deguo Liu ◽

Yajian Wang ◽

Xiu-An Yang ◽

Deyun Liu

Keyword(s):

De Novo ◽

De Novo Mutation ◽

Igf2 Gene ◽

Silver Russell Syndrome

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Chromosome-Level Assembly of Drosophila bifasciata Reveals Important Karyotypic Transition of the X Chromosome

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400922 ◽

2020 ◽

Vol 10 (3) ◽

pp. 891-897 ◽

Cited By ~ 3

Author(s):

Ryan Bracewell ◽

Anita Tran ◽

Kamalakar Chatla ◽

Doris Bachtrog

Keyword(s):

X Chromosome ◽

Genome Assembly ◽

De Novo ◽

Pericentromeric Region ◽

Species Group ◽

Chromosome 15 ◽

Protein Coding ◽

Protein Coding Genes ◽

Long Read ◽

Chromosome Level

The Drosophila obscura species group is one of the most studied clades of Drosophila and harbors multiple distinct karyotypes. Here we present a de novo genome assembly and annotation of D. bifasciata, a species which represents an important subgroup for which no high-quality chromosome-level genome assembly currently exists. We combined long-read sequencing (Nanopore) and Hi-C scaffolding to achieve a highly contiguous genome assembly approximately 193 Mb in size, with repetitive elements constituting 30.1% of the total length. Drosophila bifasciata harbors four large metacentric chromosomes and the small dot, and our assembly contains each chromosome in a single scaffold, including the highly repetitive pericentromeres, which were largely composed of Jockey and Gypsy transposable elements. We annotated a total of 12,821 protein-coding genes and comparisons of synteny with D. athabasca orthologs show that the large metacentric pericentromeric regions of multiple chromosomes are conserved between these species. Importantly, Muller A (X chromosome) was found to be metacentric in D. bifasciata and the pericentromeric region appears homologous to the pericentromeric region of the fused Muller A-AD (XL and XR) of pseudoobscura/affinis subgroup species. Our finding suggests a metacentric ancestral X fused to a telocentric Muller D and created the large neo-X (Muller A-AD) chromosome ∼15 MYA. We also confirm the fusion of Muller C and D in D. bifasciata and show that it likely involved a centromere-centromere fusion.

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