TY - JOUR
T1 - Flanking variation influences rates of stutter in simple repeats
AU - Woerner, August E.
AU - King, Jonathan L.
AU - Budowle, Bruce
N1 - Funding Information:
Acknowledgments: This work was supported in part by award no. 2015-DN-BX-K067, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice.
Publisher Copyright:
© 2017 by the authors.
PY - 2017/11/17
Y1 - 2017/11/17
N2 - It has been posited that the longest uninterrupted stretch (LUS) of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL). While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.
AB - It has been posited that the longest uninterrupted stretch (LUS) of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL). While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.
KW - Flanking variation
KW - Longest uninterrupted stretch (LUS)
KW - Parental allele length (PAL)
KW - Short tandem repeats (STR)
KW - Stutter
UR - http://www.scopus.com/inward/record.url?scp=85034739286&partnerID=8YFLogxK
U2 - 10.3390/genes8110329
DO - 10.3390/genes8110329
M3 - Article
AN - SCOPUS:85034739286
SN - 2073-4425
VL - 8
JO - Genes
JF - Genes
IS - 11
M1 - 329
ER -