The A1555G mutation in the 12S rRNA gene of human mtDNA

Recurrent origins and founder events in families affected by sensorineural deafness

Antonio Torroni, Fulvio Cruciani, Chiara Rengo, Daniele Sellitto, Núria López-Bigas, Raquel Rabionet, Nancy Govea, Adolfo López De Munain, Maritza Sarduy, Lourdes Romero, Manuela Villamar, Ignacio Del Castillo, Felipe Moreno, Xavier P. Estivill, Rosaria Scozzari

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ≥30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from pre-symptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

Original languageEnglish
Pages (from-to)1349-1358
Number of pages10
JournalAmerican Journal of Human Genetics
Volume65
Issue number5
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Deafness
Mitochondrial DNA
rRNA Genes
Mutation
Population Control
Selection Bias
Sensorineural Hearing Loss
Aminoglycosides
Mutation Rate
Restriction Fragment Length Polymorphisms
Spain
Haplotypes
Population
ribosomal RNA 12S

ASJC Scopus subject areas

  • Genetics

Cite this

The A1555G mutation in the 12S rRNA gene of human mtDNA : Recurrent origins and founder events in families affected by sensorineural deafness. / Torroni, Antonio; Cruciani, Fulvio; Rengo, Chiara; Sellitto, Daniele; López-Bigas, Núria; Rabionet, Raquel; Govea, Nancy; López De Munain, Adolfo; Sarduy, Maritza; Romero, Lourdes; Villamar, Manuela; Del Castillo, Ignacio; Moreno, Felipe; Estivill, Xavier P.; Scozzari, Rosaria.

In: American Journal of Human Genetics, Vol. 65, No. 5, 1999, p. 1349-1358.

Research output: Contribution to journalArticle

Torroni, A, Cruciani, F, Rengo, C, Sellitto, D, López-Bigas, N, Rabionet, R, Govea, N, López De Munain, A, Sarduy, M, Romero, L, Villamar, M, Del Castillo, I, Moreno, F, Estivill, XP & Scozzari, R 1999, 'The A1555G mutation in the 12S rRNA gene of human mtDNA: Recurrent origins and founder events in families affected by sensorineural deafness', American Journal of Human Genetics, vol. 65, no. 5, pp. 1349-1358. https://doi.org/10.1086/302642
Torroni, Antonio ; Cruciani, Fulvio ; Rengo, Chiara ; Sellitto, Daniele ; López-Bigas, Núria ; Rabionet, Raquel ; Govea, Nancy ; López De Munain, Adolfo ; Sarduy, Maritza ; Romero, Lourdes ; Villamar, Manuela ; Del Castillo, Ignacio ; Moreno, Felipe ; Estivill, Xavier P. ; Scozzari, Rosaria. / The A1555G mutation in the 12S rRNA gene of human mtDNA : Recurrent origins and founder events in families affected by sensorineural deafness. In: American Journal of Human Genetics. 1999 ; Vol. 65, No. 5. pp. 1349-1358.
@article{676f188c4ae543b6a1342f87155d16bc,
title = "The A1555G mutation in the 12S rRNA gene of human mtDNA: Recurrent origins and founder events in families affected by sensorineural deafness",
abstract = "The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ≥30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from pre-symptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.",
author = "Antonio Torroni and Fulvio Cruciani and Chiara Rengo and Daniele Sellitto and N{\'u}ria L{\'o}pez-Bigas and Raquel Rabionet and Nancy Govea and {L{\'o}pez De Munain}, Adolfo and Maritza Sarduy and Lourdes Romero and Manuela Villamar and {Del Castillo}, Ignacio and Felipe Moreno and Estivill, {Xavier P.} and Rosaria Scozzari",
year = "1999",
doi = "10.1086/302642",
language = "English",
volume = "65",
pages = "1349--1358",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - The A1555G mutation in the 12S rRNA gene of human mtDNA

T2 - Recurrent origins and founder events in families affected by sensorineural deafness

AU - Torroni, Antonio

AU - Cruciani, Fulvio

AU - Rengo, Chiara

AU - Sellitto, Daniele

AU - López-Bigas, Núria

AU - Rabionet, Raquel

AU - Govea, Nancy

AU - López De Munain, Adolfo

AU - Sarduy, Maritza

AU - Romero, Lourdes

AU - Villamar, Manuela

AU - Del Castillo, Ignacio

AU - Moreno, Felipe

AU - Estivill, Xavier P.

AU - Scozzari, Rosaria

PY - 1999

Y1 - 1999

N2 - The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ≥30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from pre-symptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

AB - The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ≥30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from pre-symptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

UR - http://www.scopus.com/inward/record.url?scp=0033361927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033361927&partnerID=8YFLogxK

U2 - 10.1086/302642

DO - 10.1086/302642

M3 - Article

VL - 65

SP - 1349

EP - 1358

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -