Section: Evolutionary Biology
Topic: Evolution, Genetics/Genomics

Deceptive combined effects of short allele dominance and stuttering: an example with Ixodes scapularis, the main vector of Lyme disease in the U.S.A.

Corresponding author(s): De Meeûs, Thierry (thierry.demeeus@ird.fr)

10.24072/pcjournal.34 - Peer Community Journal, Volume 1 (2021), article no. e40.

Get full text PDF Peer reviewed and recommended by PCI
article image

Null alleles, short allele dominance (SAD), and stuttering increase the perceived relative inbreeding of individuals and subpopulations as measured by Wrights F_IS and F_ST. Ascertainment bias, due to such amplifying problems are usually caused by inaccurate primer design (if developed from a different species or a distant population), poor DNA quality, low DNA concentration, or a combination of some or all these sources of inaccuracy. When combined, these issues can increase the correlation between polymorphism at concerned loci and, consequently, of linkage disequilibrium (LD) between those. In this note, we studied an original microsatellite data set generated by analyzing nine loci in Ixodes scapularis ticks from the eastern U.S.A. To detect null alleles and SAD we used correlation methods and variation measures. To detect stuttering, we evaluated heterozygote deficit between alleles displaying a single repeat difference. We demonstrated that an important proportion of loci affected by amplification problems (one with null alleles, two with SAD and three with stuttering) lead to highly significant heterozygote deficits (F_IS=0.1, p-value<0.0001). This occurred together with an important proportion (22%) of pairs of loci in significant LD, two of which were still significant after a false discovery rate (FDR) correction, and some variation in the measurement of population subdivision across loci (Wrights F_ST). This suggested a strong Wahlund effect and/or selection at several loci. By finding small peaks corresponding to previously disregarded larger alleles in some homozygous profiles for loci with SAD and by pooling alleles close in size for loci with stuttering, we generated an amended dataset. Except for one locus with null alleles and another still displaying a modest SAD, the analyses of the corrected dataset revealed a significant excess of heterozygotes (F_IS=-0.07 as expected in dioecious and strongly subdivided populations, with a more reasonable proportion (19%) of pairs of loci characterized by significant LD, none of which stayed significant after the FDR procedure. Strong subdivision was also confirmed by the standardized F_ST corrected for null alleles (F_ST=0.19) and small effective subpopulation sizes (N_e=7).

Published online:
DOI: 10.24072/pcjournal.34
Type: Research article

De Meeûs, Thierry 1; Chan, Cynthia T. 2, 3, 4; Ludwig, John M. 5, 4; Tsao, Jean I. 6; Patel, Jaymin 7, 4; Bhagatwala, Jigar 8, 4; Beati, Lorenza 4

1 Intertryp, IRD, Cirad, Univ Montpellier, Montpellier, France
2 Boehringer Ingelheim, Athens, GA, USA
3 College of Agricultural & Environmental Sciences, University of Georgia, Athens, GA, USA
4 The U.S. National Tick Collection, Institute for Coastal Plain Science, Georgia Southern University, Statesboro, GA, USA
5 Institute of Bioinformatics, University of Georgia, Athens, GA, USA
6 Department of Fisheries and Wildlife, Department of Large Animal Clinical Sciences, Ecology, Evolutionary Biology and Behavior, Michigan State University, East Lansing, MI, USA
7 Division of Hospital Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
8 Medical College of Georgia, Augusta University, Augusta, GA, USA
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights
@article{10_24072_pcjournal_34,
     author = {De Mee\^us, Thierry and Chan, Cynthia T. and Ludwig, John M. and Tsao, Jean I. and Patel, Jaymin and Bhagatwala, Jigar and Beati, Lorenza},
     title = {Deceptive combined effects of short allele dominance and stuttering: an example with {\protect\emph{Ixodes} scapularis}, the main vector of {Lyme} disease in the {U.S.A.}},
     journal = {Peer Community Journal},
     eid = {e40},
     publisher = {Peer Community In},
     volume = {1},
     year = {2021},
     doi = {10.24072/pcjournal.34},
     url = {https://peercommunityjournal.org/articles/10.24072/pcjournal.34/}
}
TY  - JOUR
AU  - De Meeûs, Thierry
AU  - Chan, Cynthia T.
AU  - Ludwig, John M.
AU  - Tsao, Jean I.
AU  - Patel, Jaymin
AU  - Bhagatwala, Jigar
AU  - Beati, Lorenza
TI  - Deceptive combined effects of short allele dominance and stuttering: an example with Ixodes scapularis, the main vector of Lyme disease in the U.S.A.
JO  - Peer Community Journal
PY  - 2021
VL  - 1
PB  - Peer Community In
UR  - https://peercommunityjournal.org/articles/10.24072/pcjournal.34/
DO  - 10.24072/pcjournal.34
ID  - 10_24072_pcjournal_34
ER  - 
%0 Journal Article
%A De Meeûs, Thierry
%A Chan, Cynthia T.
%A Ludwig, John M.
%A Tsao, Jean I.
%A Patel, Jaymin
%A Bhagatwala, Jigar
%A Beati, Lorenza
%T Deceptive combined effects of short allele dominance and stuttering: an example with Ixodes scapularis, the main vector of Lyme disease in the U.S.A.
%J Peer Community Journal
%D 2021
%V 1
%I Peer Community In
%U https://peercommunityjournal.org/articles/10.24072/pcjournal.34/
%R 10.24072/pcjournal.34
%F 10_24072_pcjournal_34
De Meeûs, Thierry; Chan, Cynthia T.; Ludwig, John M.; Tsao, Jean I.; Patel, Jaymin; Bhagatwala, Jigar; Beati, Lorenza. Deceptive combined effects of short allele dominance and stuttering: an example with Ixodes scapularis, the main vector of Lyme disease in the U.S.A.. Peer Community Journal, Volume 1 (2021), article  no. e40. doi : 10.24072/pcjournal.34. https://peercommunityjournal.org/articles/10.24072/pcjournal.34/

PCI peer reviews and recommendation, and links to data, scripts, code and supplementary information: 10.24072/pci.evolbiol.100081

Conflict of interest of the recommender and peer reviewers:
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

[1] Balloux, F. Heterozygote excess in small populations and the heterozygote-excess effective population size, Evolution, Volume 58 (2004) no. 9, pp. 1891-1900 | DOI

[2] Beati, L.; Keirans, J. E. Analysis of the Systematic Relationships among Ticks of the Genera Rhipicephalus and Boophilus (Acari: Ixodidae) Based on Mitochondrial 12S Ribosomal DNA Gene Sequences and Morphological Characters, The Journal of Parasitology, Volume 87 (2001) no. 1 | DOI

[3] Benjamini, Y.; Hochberg, Y. On the Adaptive Control of the False Discovery Rate in Multiple Testing With Independent Statistics, Journal of Educational and Behavioral Statistics, Volume 25 (2000) no. 1, pp. 60-83 | DOI

[4] Benjamini, Y.; Yekutieli, D. The control of the false discovery rate in multiple testing under dependency, The Annals of Statistics, Volume 29 (2001) no. 4 | DOI

[5] Castle, W. E. The Laws of Heredity of Galton and Mendel, and Some Laws Governing Race Improvement by Selection, Proceedings of the American Academy of Arts and Sciences, Volume 39 (1903) no. 8 | DOI

[6] Chapuis, M.-P.; Estoup, A. Microsatellite Null Alleles and Estimation of Population Differentiation, Molecular Biology and Evolution, Volume 24 (2007) no. 3, pp. 621-631 | DOI

[7] Coombs, J. A.; Letcher, B. H.; Nislow, K. H. create: a software to create input files from diploid genotypic data for 52 genetic software programs, Molecular Ecology Resources, Volume 8 (2008) no. 3, pp. 578-580 | DOI

[8] De Meeûs, T. Initiation à la génétique des populations naturelles, IRD Éditions, 2012 | DOI

[9] De Meeûs, T. Revisiting FIS, FST, Wahlund Effects, and Null Alleles, Journal of Heredity, Volume 109 (2018) no. 4, pp. 446-456 | DOI

[10] de Meeûs, T.; Béati, L.; Delaye, C.; Aeschlimann, A.; Renaud, F. Sex-biased genetic structure in the vector of lyme disease, ixodes ricinus, Evolution, Volume 56 (2002) no. 9 | DOI

[11] De Meeûs, T.; Guégan, J.-F.; Teriokhin, A. T. MultiTest V.1.2, a program to binomially combine independent tests and performance comparison with other related methods on proportional data, BMC Bioinformatics, Volume 10 (2009) no. 1 | DOI

[12] de Meeûs, T.; Humair, P.-F.; Grunau, C.; Delaye, C.; Renaud, F. Non-Mendelian transmission of alleles at microsatellite loci: an example in Ixodes ricinus, the vector of Lyme disease, International Journal for Parasitology, Volume 34 (2004) no. 8, pp. 943-950 | DOI

[13] de Meeûs, T.; McCoy, K. D.; Prugnolle, F.; Chevillon, C.; Durand, P.; Hurtrez-Boussès, S.; Renaud, F. Population genetics and molecular epidemiology or how to “débusquer la bête”, Infection, Genetics and Evolution, Volume 7 (2007) no. 2, pp. 308-332 | DOI

[14] Delaye, C.; Aeschlimann, A.; Renaud, F.; Rosenthal, B.; De Meeûs, T. Isolation and characterization of microsatellite markers in the Ixodes ricinus complex (Acari : Ixodidae), Molecular Ecology, Volume 7 (1998) no. 3, pp. 357-363 | DOI

[15] Delaye, C.; Béati, L.; Aeschlimann, A.; Renaud, F.; De Meeûs, T. Population genetic structure of Ixodes ricinus in Switzerland from allozymic data: No evidence of divergence between nearby sites, International Journal for Parasitology, Volume 27 (1997) no. 7, pp. 769-773 | DOI

[16] Fagerberg, A. J.; Fulton, R. E.; Black Iv, W. C. Microsatellite loci are not abundant in all arthropod genomes: analyses in the hard tick,Ixodes scapularisand the yellow fever mosquito,Aedes aegypti, Insect Molecular Biology, Volume 10 (2001) no. 3, pp. 225-236 | DOI

[17] Fox, J. The R Commander: A Basic-Statistics Graphical User Interface toR, Journal of Statistical Software, Volume 14 no. 9 | DOI

[18] Fox, J. Extending the R commander by "plug in" packages, R News, Volume 7 (2007)

[19] Frantz, A. C.; Cellina, S.; Krier, A.; Schley, L.; Burke, T. Using spatial Bayesian methods to determine the genetic structure of a continuously distributed population: clusters or isolation by distance?, Journal of Applied Ecology, Volume 46 (2009) no. 2, pp. 493-505 | DOI

[20] Goudet, J. FSTAT (Version 1.2): A Computer Program to Calculate F-Statistics, Journal of Heredity, Volume 86 (1995) no. 6, pp. 485-486 | DOI

[21] Goudet, J. Fstat (ver. 2.9.4), a program to estimate and test population genetics parameters. Available at http://www.t-de-meeus.fr/Programs/Fstat294.zip, Updated from Goudet (1995)., 2003

[22] Goudet, J.; Raymond, M.; de Meeüs, T.; Rousset, F. Testing Differentiation in Diploid Populations, Genetics, Volume 144 (1996) no. 4, pp. 1933-1940 | DOI

[23] Gulia-Nuss, M.; Nuss, A. B.; Meyer, J. M.; Sonenshine, D. E.; Roe, R. M.; Waterhouse, R. M.; Sattelle, D. B.; de la Fuente, J.; Ribeiro, J. M.; Megy, K.; Thimmapuram, J.; Miller, J. R.; Walenz, B. P.; Koren, S.; Hostetler, J. B.; Thiagarajan, M.; Joardar, V. S.; Hannick, L. I.; Bidwell, S.; Hammond, M. P.; Young, S.; Zeng, Q.; Abrudan, J. L.; Almeida, F. C.; Ayllón, N.; Bhide, K.; Bissinger, B. W.; Bonzon-Kulichenko, E.; Buckingham, S. D.; Caffrey, D. R.; Caimano, M. J.; Croset, V.; Driscoll, T.; Gilbert, D.; Gillespie, J. J.; Giraldo-Calderón, G. I.; Grabowski, J. M.; Jiang, D.; Khalil, S. M. S.; Kim, D.; Kocan, K. M.; Koči, J.; Kuhn, R. J.; Kurtti, T. J.; Lees, K.; Lang, E. G.; Kennedy, R. C.; Kwon, H.; Perera, R.; Qi, Y.; Radolf, J. D.; Sakamoto, J. M.; Sánchez-Gracia, A.; Severo, M. S.; Silverman, N.; Šimo, L.; Tojo, M.; Tornador, C.; Van Zee, J. P.; Vázquez, J.; Vieira, F. G.; Villar, M.; Wespiser, A. R.; Yang, Y.; Zhu, J.; Arensburger, P.; Pietrantonio, P. V.; Barker, S. C.; Shao, R.; Zdobnov, E. M.; Hauser, F.; Grimmelikhuijzen, C. J. P.; Park, Y.; Rozas, J.; Benton, R.; Pedra, J. H. F.; Nelson, D. R.; Unger, M. F.; Tubio, J. M. C.; Tu, Z.; Robertson, H. M.; Shumway, M.; Sutton, G.; Wortman, J. R.; Lawson, D.; Wikel, S. K.; Nene, V. M.; Fraser, C. M.; Collins, F. H.; Birren, B.; Nelson, K. E.; Caler, E.; Hill, C. A. Genomic insights into the Ixodes scapularis tick vector of Lyme disease, Nature Communications, Volume 7 (2016) no. 1 | DOI

[24] Hardy, G. H. Mendelian Proportions in a Mixed Population, Science, Volume 28 (1908) no. 706, pp. 49-50 | DOI

[25] Hedrick, P. W. Perspective: Highly Variable Loci and Their Interpretation in Evolution and Conservation, Evolution, Volume 53 (1999) no. 2 | DOI

[26] Jombart, T.; Devillard, S.; Balloux, F. Discriminant analysis of principal components: a new method for the analysis of genetically structured populations, BMC Genetics, Volume 11 (2010) no. 1 | DOI

[27] Kaboré, J.; MacLeod, A.; Jamonneau, V.; Ilboudo, H.; Duffy, C.; Camara, M.; Camara, O.; Belem, A. M. G.; Bucheton, B.; De Meeûs, T. Population genetic structure of Guinea Trypanosoma brucei gambiense isolates according to host factors, Infection, Genetics and Evolution, Volume 11 (2011) no. 5, pp. 1129-1135 | DOI

[28] Kaeuffer, R.; Réale, D.; Coltman, D. W.; Pontier, D. Detecting population structure using STRUCTURE software: effect of background linkage disequilibrium, Heredity, Volume 99 (2007) no. 4, pp. 374-380 | DOI

[29] Keirans, J. E.; Needham, G. R.; Oliver, J. H. The Ixodes (Ixodes) ricinus complex worldwide. Diagnosis of the species in the complex, hosts and distribution In: Needham, G.R. R. M. , Horn, D.J. , Welbourn, W.C. (Eds.), Acarology IX: Symposia. (1999), pp. 341-347

[30] Kempf, F.; De Meeûs, T.; Vaumourin, E.; Noel, V.; Taragel’ová, V.; Plantard, O.; Heylen, D. J.; Eraud, C.; Chevillon, C.; McCoy, K. D. Host races in Ixodes ricinus, the European vector of Lyme borreliosis, Infection, Genetics and Evolution, Volume 11 (2011) no. 8, pp. 2043-2048 | DOI

[31] Kempf, F.; McCoy, K. D.; De Meeûs, T. Wahlund effects and sex-biased dispersal in Ixodes ricinus, the European vector of Lyme borreliosis: New tools for old data, Infection, Genetics and Evolution, Volume 10 (2010) no. 7, pp. 989-997 | DOI

[32] Latch, E. K.; Dharmarajan, G.; Glaubitz, J. C.; Rhodes, O. E. Relative performance of Bayesian clustering software for inferring population substructure and individual assignment at low levels of population differentiation, Conservation Genetics, Volume 7 (2006) no. 2, pp. 295-302 | DOI

[33] Manangwa, O.; De Meeûs, T.; Grébaut, P.; Ségard, A.; Byamungu, M.; Ravel, S. Detecting Wahlund effects together with amplification problems: Cryptic species, null alleles and short allele dominance inGlossina pallidipespopulations from Tanzania, Molecular Ecology Resources, Volume 19 (2019) no. 3, pp. 757-772 | DOI

[34] Meirmans, P. G. Seven common mistakes in population genetics and how to avoid them, Molecular Ecology, Volume 24 (2015) no. 13, pp. 3223-3231 | DOI

[35] Nei, M.; Chesser, R. K. Estimation of fixation indices and gene diversities, Annals of Human Genetics, Volume 47 (1983) no. 3, pp. 253-259 | DOI

[36] Norris, D. E.; Klompen, J.; Keirans, J. E.; Black, W. C. Population Genetics of Ixodes scapularis (Acari: Ixodidae) Based on Mitochondrial 16S and 12S Genes, Journal of Medical Entomology, Volume 33 (1996) no. 1, pp. 78-89 | DOI

[37] Qiu, W.-G.; Dykhuizen, D. E.; Acosta, M. S.; Luft, B. J. Geographic Uniformity of the Lyme Disease Spirochete (Borrelia burgdorferi) and Its Shared History With Tick Vector (Ixodes scapularis) in the Northeastern United States, Genetics, Volume 160 (2002) no. 3, pp. 833-849 | DOI

[38] R Core Team R: A Language and Environment for Statistical Computing, Version 3.5.0 (2018-04-23) Ed. R Foundation for Statistical Computing, Vienna, Austria, http://www.R-project.org., 2018

[39] Rousset, F. Equilibrium Values of Measures of Population Subdivision for Stepwise Mutation Processes, Genetics, Volume 142 (1996) no. 4, pp. 1357-1362 | DOI

[40] Rulison, E. L.; Kuczaj, I.; Pang, G.; Hickling, G. J.; Tsao, J. I.; Ginsberg, H. S. Flagging versus dragging as sampling methods for nymphalIxodes scapularis(Acari: Ixodidae), Journal of Vector Ecology, Volume 38 (2013) no. 1, pp. 163-167 | DOI

[41] Sakamoto, J. M.; Goddard, J.; Rasgon, J. L. Population and Demographic Structure of Ixodes scapularis Say in the Eastern United States, PLoS ONE, Volume 9 (2014) no. 7 | DOI

[42] Séré, M.; Thévenon, S.; Belem, A. M. G.; De Meeûs, T. Comparison of different genetic distances to test isolation by distance between populations, Heredity, Volume 119 (2017) no. 2, pp. 55-63 | DOI

[43] Séré, M.; Thévenon, S.; Belem, A. M. G.; De Meeûs, T. Comparison of different genetic distances to test isolation by distance between populations, Heredity, Volume 119 (2017) no. 2, pp. 55-63 | DOI

[44] Van Oosterhout, C.; Hutchinson, W. F.; Wills, D. P. M.; Shipley, P. micro-checker: software for identifying and correcting genotyping errors in microsatellite data, Molecular Ecology Notes, Volume 4 (2004) no. 3, pp. 535-538 | DOI

[45] Wang, C.; Schroeder, K. B.; Rosenberg, N. A. A Maximum-Likelihood Method to Correct for Allelic Dropout in Microsatellite Data with No Replicate Genotypes, Genetics, Volume 192 (2012) no. 2, pp. 651-669 | DOI

[46] Waples, R. S. A bias correction for estimates of effective population size based on linkage disequilibrium at unlinked gene loci*, Conservation Genetics, Volume 7 (2006) no. 2, pp. 167-184 | DOI

[47] Waples, R. S. Testing for Hardy–Weinberg Proportions: Have We Lost the Plot?, Journal of Heredity, Volume 106 (2015) no. 1, pp. 1-19 | DOI

[48] Waples, R. S. Null Alleles and FIS × FST Correlations, Journal of Heredity, Volume 109 (2018) no. 4, pp. 457-461 | DOI

[49] Waples, R. S.; Do, C. Linkage disequilibrium estimates of contemporaryNeusing highly variable genetic markers: a largely untapped resource for applied conservation and evolution, Evolutionary Applications, Volume 3 (2010) no. 3, pp. 244-262 | DOI

[50] Wattier, R.; Engel, C. R.; Saumitou‐Laprade, P.; Valero, M. Short allele dominance as a source of heterozygote deficiency at microsatellite loci: experimental evidence at the dinucleotide locus Gv1CT inGracilaria gracilis(Rhodophyta), Molecular Ecology, Volume 7 (1998) no. 11, pp. 1569-1573 | DOI

[51] Weinberg, W. Über den Nachweis der Verebung beim Menschen, Jahresheft des Vereins fur Vaterlundische Naturkunde in Wurttemberg, Volume 64 (1908)

[52] Weir, B. S.; Cockerham, C. C. Estimating F-Statistics for the Analysis of Population Structure, Evolution, Volume 38 (1984) no. 6 | DOI

[53] Wright, S. The Interpretation of Population Structure by F-Statistics with Special Regard to Systems of Mating, Evolution, Volume 19 (1965) no. 3 | DOI

[54] Yuval, B.; Spielman, A. Duration and Regulation of the Developmental Cycle of Ixodes dammini (Acari: Ixodidae), Journal of Medical Entomology, Volume 27 (1990) no. 2, pp. 196-201 | DOI

Cited by Sources:

block.super