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Investigation of the origins of human autosomal inversions

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Abstract

A significant proportion of both pericentric and paracentric inversions have recurrent breakpoints and so could either have arisen through multiple independent events or be identical by descent (IBD) with a single common ancestor. Of two common variant inversions previously studied, the inv(2)(p11q13) was genuinely recurrent while the inv(10)(p11.2q21.2) was IBD in all cases tested. Excluding these two variants we have ascertained 257 autosomal inversion probands at the Wessex Regional Genetics Laboratory. There were 104 apparently recurrent inversions, representing 35 different breakpoint combinations and we speculated that at least some of these had arisen on more than one occasion. However, haplotype analysis identified no recurrent cases among eight inversions tested, including the variant inv(5)(p13q13). The cases not IBD were shown to have different breakpoints at the molecular cytogenetic level. No crossing over was detected within any of the inversions and the founder haplotypes extended for variable distances beyond the inversion breakpoints. Defining breakpoint intervals by FISH mapping identified no obvious predisposing elements in the DNA sequence. In summary the vast majority of human inversions arise as unique events. Even apparently recurrent inversions, with the exception of the inv(2)(p12q13), are likely to be either derived from a common ancestor or to have subtly different breakpoints. Presumably the lack of selection against most inversions allows them to accumulate and disperse amongst different populations over time.

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Acknowledgments

We are very grateful to Mrs. Barbara O’Prey for obtaining patient samples and Dr. Katherine Lachlan for supplying clinical information for phenotype–genotype correlations. Dr. Claire Scott (claire.scott@orh.nhs.uk) kindly provided inversion data from the Chromosome Abnormality Database (funded by BDF Newlife) and additional DNA samples were obtained from Dr. Leema Robert and Dr. Caroline MacKie-Ogilvie.

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Authors and Affiliations

  1. Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, SP2 8BJ, UK

    N. Simon Thomas, Annette E. Cockwell & Patricia A. Jacobs

  2. Department of Human Genetics, University of Southampton, Southampton, UK

    N. Simon Thomas, Victoria Bryant & Patricia A. Jacobs

  3. National Genetics Reference Laboratory (Wessex), Salisbury District Hospital, Salisbury, SP2 8BJ, UK

    Vivienne Maloney

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  1. N. Simon Thomas
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  2. Victoria Bryant
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  3. Vivienne Maloney
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  4. Annette E. Cockwell
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  5. Patricia A. Jacobs
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Correspondence to N. Simon Thomas.

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Thomas, N.S., Bryant, V., Maloney, V. et al. Investigation of the origins of human autosomal inversions. Hum Genet 123, 607–616 (2008). https://doi.org/10.1007/s00439-008-0510-z

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  • DOI: https://doi.org/10.1007/s00439-008-0510-z

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