Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

Elisabeth M Lodder; Bert H Eussen; Daniëlla A C M van Hassel; A Jeannette M Hoogeboom; Pino J Poddighe; J Henk Coert; Ben A Oostra; Annelies de Klein; Esther de Graaff

doi:10.1007/s10577-009-9059-5

Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

Elisabeth M Lodder, Bert H Eussen, Daniëlla A C M van Hassel, A Jeannette M Hoogeboom, Pino J Poddighe, J Henk Coert, Ben A Oostra, Annelies de Klein, Esther de Graaff

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient.

Original language	English
Pages (from-to)	737-44
Number of pages	8
Journal	Chromosome Research
Volume	17
Issue number	6
DOIs	https://doi.org/10.1007/s10577-009-9059-5
Publication status	Published - 2009
Externally published	Yes

Keywords

Base Sequence
Blotting, Southern
Chromosome Breakage
Chromosome Inversion
Chromosomes, Human, Pair 7/genetics
Chromosomes, Human, Y/genetics
Foot Deformities, Congenital/genetics
Gene Expression Profiling
Gene Expression Regulation
Hand Deformities, Congenital/genetics
Homeodomain Proteins/genetics
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
Polydactyly/genetics
RNA, Messenger/genetics
Reverse Transcriptase Polymerase Chain Reaction

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title = "Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly",

abstract = "Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient.",

keywords = "Base Sequence, Blotting, Southern, Chromosome Breakage, Chromosome Inversion, Chromosomes, Human, Pair 7/genetics, Chromosomes, Human, Y/genetics, Foot Deformities, Congenital/genetics, Gene Expression Profiling, Gene Expression Regulation, Hand Deformities, Congenital/genetics, Homeodomain Proteins/genetics, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Polydactyly/genetics, RNA, Messenger/genetics, Reverse Transcriptase Polymerase Chain Reaction",

author = "Lodder, {Elisabeth M} and Eussen, {Bert H} and {van Hassel}, {Dani{\"e}lla A C M} and Hoogeboom, {A Jeannette M} and Poddighe, {Pino J} and Coert, {J Henk} and Oostra, {Ben A} and {de Klein}, Annelies and {de Graaff}, Esther",

year = "2009",

doi = "10.1007/s10577-009-9059-5",

language = "English",

volume = "17",

pages = "737--44",

journal = "Chromosome Research",

issn = "0967-3849",

publisher = "Springer",

number = "6",

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T1 - Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

AU - Lodder, Elisabeth M

AU - Eussen, Bert H

AU - van Hassel, Daniëlla A C M

AU - Hoogeboom, A Jeannette M

AU - Poddighe, Pino J

AU - Coert, J Henk

AU - Oostra, Ben A

AU - de Klein, Annelies

AU - de Graaff, Esther

PY - 2009

Y1 - 2009

N2 - Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient.

AB - Apparently balanced chromosomal inversions may lead to disruption of developmentally important genes at the breakpoints of the inversion, causing congenital malformations. Characterization of such inversions may therefore lead to new insights in human development. Here, we report on a de novo inversion of chromosome 7 (p15.2q36.3) in a patient with postaxial polysyndactyly. The breakpoints do not disrupt likely candidate genes for the limb phenotype observed in the patient. However, on the p-arm the breakpoint separates the HOXA cluster from a gene desert containing several conserved noncoding elements, suggesting that a disruption of a cis-regulatory circuit of the HOXA cluster could be the underlying cause of the phenotype in this patient.

KW - Base Sequence

KW - Blotting, Southern

KW - Chromosome Breakage

KW - Chromosome Inversion

KW - Chromosomes, Human, Pair 7/genetics

KW - Chromosomes, Human, Y/genetics

KW - Foot Deformities, Congenital/genetics

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Hand Deformities, Congenital/genetics

KW - Homeodomain Proteins/genetics

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Karyotyping

KW - Molecular Sequence Data

KW - Oligonucleotide Array Sequence Analysis

KW - Polydactyly/genetics

KW - RNA, Messenger/genetics

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1007/s10577-009-9059-5

DO - 10.1007/s10577-009-9059-5

M3 - Article

C2 - 19672683

SN - 0967-3849

VL - 17

SP - 737

EP - 744

JO - Chromosome Research

JF - Chromosome Research

IS - 6

ER -

Implication of long-distance regulation of the HOXA cluster in a patient with postaxial polydactyly

Abstract

Keywords

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