BMC Medical Genetics - Latest Comments

Clarification needed

Dan T.A. Eisenberg — 2013-02-19T17:18:37Z

In a scientific literature which is dominated by studies of peoples of western European descent (Bustamante and others, 2011; Henrich and others, 2010), the work of Al-Attas et al to better understand the diversity of human biology and genetics is particularly valuable. However, reading Al-Attas and colleagues manuscript leaves several questions and points of confusion for me which make it hard to contextualize it within the broader literature on telomere biology.

First, in the separate analyses of maternal and paternal heritability of telomere length, the sample sizes that these statistics are based on are not clear. Further, what these ¿h2¿ values represent is ambiguous. They seem to be simply beta coefficients (slopes) between a single parents and a child, but are reported as ¿h2¿ values, which should be twice the single-parent beta coefficient (or equal to the midparental beta co-efficient). Some clarity would be useful here. Since previous studies examining sex-specific heritability patterns of telomere length have used correlation coefficients rather than beta values, it would also be helpful to have these correlation coefficient statistics reported so these results can be compared with past studies.

Second, I have some questions about the laboratory methods used to determine telomere length. A qPCR method was used, but then telomere length measurements are given in kilobases with no explanation for how such a conversion was conducted or how reliable this conversion is. As well, the coefficient of variation across replicate samples is not given as it should be if we are to evaluate the quality of these data.

I hope Al-Attas and colleagues can answer these questions so as to increase the value of their findings for the scientific literature.

References

Bustamante CD, De La Vega FM, Burchard EG. 2011. Genomics for the world. Nature 475(7355):163-165.
Henrich J, Heine SJ, Norenzayan A. 2010. Most people are not WEIRD. Nature 466(7302):29-29.

Mistake detected in our article

María Piedra — 2013-01-14T10:32:52Z

We have detected a mistake in the Methods section of our article. In the study of the 245 T/G SNP of the OPG where we wrote "rs3134070" we must have written " rs3134069". We want to apologize for any inconvenience we have caused to any person who have read our paper.

Note while in press

Anat Erdreich-Epstein — 2012-04-25T14:40:15Z

While this manuscript was in press, a paper was published by Reiter et al (Eur J Oral Sci. 2012, 120(2):97-103. doi: 10.1111) in which they found that patients with submucous cleft palate had increased allele frequency at SNP rs5752638 of the gene MN1 compared to control individuals. This further supports a possible role for MN1 in cleft palate biology.

Error of the nomenclature of the mutation described by Nordling et al.

Daniele MULLER — 2011-11-03T14:48:00Z

The name of the mutation described by Nordling et al.,1998 (Ref 13) should be (p.Ser93Glu106delinsPro) instead of (p.Ser98Glu106delinsPro).

Approximate -derivations and approximate quadratic -derivations on C*-algebras

Choonkil Park — 2011-10-18T15:21:51Z

(1) Between B.4.39 and B.4.40,
the following should be added
\begin{eqnarray}
\| f(a^*)-f(a)^*\| \le 4\varepsilon \|a\|^p
\end{eqnarray}
(*this one produces the equation (4.6))

(2) In B.4.40, `unique derivation' should be replaced by `unique quadartic $*$-derivation'

(3) In B.4.51, `satisfying (4.5) -- unique derivation' should be replaced by `satisfying (4.5) and (4.6) -- unique quadratic $*$-derivation'

Previous studies of ABCB1 and CYP2C19 polymorphisms in Brazilians

Guilherme Suarez-Kurtz — 2011-10-18T15:20:29Z

Santos et al. [1] reported the distribution of CYP2C19 and ABCB1 polymorphisms in Brazilians, and discussed their results with respect to European, Asian and African populations, but made no reference to previously published studies in the Brazilian population. This is particularly disconcerting in the case of the ABCB1 3435C>T SNP, since this polymorphism was first studied in Brazilians in 2002 [2]! Several subsequent articles, listed in PubMed and in the internet site of Refargen, the Brazilian Pharmacogenetics Network (http://www.refargen.org.br/gene.asp?ident=1), examined the frequency of the 3435C>T and other ABCB1 SNPs (e.g. 1236C>T and 2677G>T/A) and haplotypes in different strata of the Brazilian population [3 - 5]. The results of Santos et al. [1] for ABCB1 3435C>T in non-Amerindian sub-groups reproduce very closely these previously published data. For example, the frequency of the 3435T allele is 0.33 in the “African descent” cohort of Santos et al. [1]] versus 0.31 in self-identified black individuals in our study [5]. In this study we demonstrated that, among Brazilians, the odds of having the 3435T allele decreases with the increase of the individual proportion of the “African component of ancestry”. This provided a convincing explanation for the lower frequency of the 3435T allele in self-identified black Brazilians, compared to sub-Saharan Africans, since the estimated proportion of African ancestry in black Brazilians averages only 0.46 - 0.51 [6, 7]. Santos et al. [1] adopted this interpretation for the low frequency of ABCB1 3435T allele in their “African descent” cohort, but did not find it fit to mention our article, published in 2008 [5].
The frequency of the CYP2C19*2 and *3 polymorphisms in different strata of the Brazilian population was also publicly available [8] before Santos et al. submitted the final version of their manuscript (www.biomedcentral.com/1471-2350/12/13/prepub). Indeed, researchers associated with Refargen assessed the impact of biogeographical ancestry, self-reported “race/color” and geographical origin on the frequency distribution of CYP2C19*2, *3 and *17 in a representative cohort of the Brazilian population (n=1,034). Multinomial log-linear modeling revealed that geographical region and/or self-reported color/race had no effect on the frequency distribution of the CYP219 variant alleles [8]. The data reported by Santos et al. [1] for CYP2C19*2 in non-Amerindian sub-groups confirmed these findings, However a discrepancy is observed in relation to CYP2C19*17, which is more frequent in “African descent” than in “European descent” and “Mulatto” sub-groups studied by Santos et al [1]. These authors did not took notice of this discrepancy, but we alluded to it - duly quoting Santos et al. [1] - in a recent article on the distribution of polymorphisms in the CYP2C cluster among Amerindian populations [9] .
The approach adopted by Santos et al [1] to ignore previously published data for the ABCB1 3435C>T and CYP2C19 polymorphisms in the Brazilian population, might induce the reader to assume (wrongly) that these authors were the first to study the distribution of these clinically relevant variants among Brazilians. This assumption might be erroneously extended to other pharmacogenes, e.g. VKORC1, which Santos et al. [1] present as a distinct example of interethnic diversity using data from multinational studies [10, 11] – of which, incidentally I am co-author - but again ignoring results for their fellow countrymen. Had Santos et al. considered our articles [12, 13] they might have qualified their statement that “the contribution of VKORC1 toward (warfarin) dose requirements is higher in whites than non-whites”. We presented evidence that warfarin dose algorithms, having a VKORC1 polymorphism as the most important co-variate, perform equally well in white and black Brazilians.
A final consideration concerns “ethnic/racial” categorization: Santos et al. [1] stated that their study population was “separated in self-identified sub-groups according to ethnicity, as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects)”. I find it highly unlikely that the average Brazilian would self-identify as being of “Caucasian descent” or “African descent”. According to the “racial/ethnic” categorization used by the Brazilian Institute of Geography and Statistics (quoted by Santos et al. [1], that relies on self-perception of skin color, over 99% of Brazilians self-identify as Branco (white), Preto (black) or Pardo (meaning brown). Because these “race/color” categories correlate poorly with biogeographical ancestry of Brazilians and because most Brazilians have significant proportions of African and European ancestry, irrespective of the self-perception of “race/color” [6, 14, 15], terms such as “Caucasian descent” or “African descent” are poor descriptors of self-identified white or black Brazilians.

References

1. Santos PC, Soares RA, Santos DB, Nascimento RM, Coelho GL, Nicolau JC, Mill JG, Krieger JE, Pereira AC. CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population. BMC Med Genet 2011 Jan 19;12:13.
2. Calado RT, Falcão RP, Garcia AB, Gabellini SM, Zago MA, Franco RF. Influence of functional MDR1 gene polymorphisms on P-glycoprotein activity in CD34+ hematopoietic stem cells. Haematologica 2002, 87(6):564-568.
3. Fiegenbaum M, da Silveira FR, Van der Sand CR, Van der Sand LC, Ferreira ME, Pires RC, Hutz MH. The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin Pharmacol Ther 2005, 78(5):551-558.
4. Rodrigues AC, Rebecchi IM, Bertolami MC, Faludi AA, Hirata MH, Hirata RD. High baseline serum total and LDL cholesterol levels are associated with MDR1 haplotypes in Brazilian hypercholesterolemic individuals of European descent. Braz J Med Biol Res 2005, 38(9):1389-1397.
5. Estrela RC, Ribeiro FS, Carvalho RS, Gregório SP, Dias-Neto E, Struchiner CJ, Suarez-Kurtz G. Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture. Pharmacogenomics 2008, 9(3):267-276.
6. Suarez-Kurtz G, Pena SD. Pharmacogenomics in the Americas: the impact of genetic admixture. Curr Drug Targets 2006, 7(12):1649-1658.
7. Suarez-Kurtz G, Genro JP, de Moraes MO, Ojopi EB, Pena SD, Perini JA, Ribeiro-Dos-Santos A, Romano-Silva MA, Santana I, Struchiner CJ. Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians. Pharmacogenomics J 2010 Dec 21. [Epub ahead of print]
8. Suarez-Kurtz G. Pharmacogenetics in the Brazilian population. Front Pharmacol 2010, 1:118.
9. Vargens DD, Petzl-Erler ML, Suarez-Kurtz G. Distribution of CYP2C polymorphisms in an Amerindian population of Brazil. Basic Clin Pharm Toxicol (in press)
10. Ross KA, Bigham AW, Edwards M, Gozdzik A, Suarez-Kurtz G, Parra EJ. Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. J Hum Genet 2010, 55(9):582-589.
11. Limdi NA, Wadelius M, Cavallari L, Eriksson N, Crawford DC, Lee MT, Chen CH, Motsinger-Reif A, Sagreiya H, Liu N et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood 2010, 115(18):3827-3834.
12. Perini JA, Struchiner CJ, Silva-Assunção E, Santana IS, Rangel F, Ojopi EB, Dias-Neto E, Suarez-Kurtz G. Pharmacogenetics of warfarin: development of a dosing algorithm for Brazilian patients. Clin Pharmacol Ther 2008, 84(6):722-728.
13. Suarez-Kurtz G, Perini JA, Silva-Assunção E, Struchiner CJ. Relative contribution of VKORC1, CYP2C9, and INR response to warfarin stable dose. Blood 2009, 113(17):4125-4126.
14. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SD. Color and genomic ancestry in Brazilians. Proc Natl Acad Sci U S A 2003, 100(1):177-182.
15. Pena SD, Di Pietro G, Fuchshuber-Moraes M, Genro JP, Hutz MH, Kehdy Fde S, Kohlrausch F, Magno LA, Montenegro RC, Moraes MO et al. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS One 2011 Feb 16;6(2):e17063.

gene symbol mistypied

Dajun Deng — 2011-06-09T10:31:42Z

The gene symbol "CDNK2A" on the title should be "CDKN2A".

minor correction

Nobuaki Wakamatsu — 2011-01-14T17:20:22Z

1)"Thiamin Transport Assay" in "Methods".
"Balasubramaniem et al. [15]" should be "Ashokkumar et al. [15]"

2)Reference
8. "Am J Physiol Renal Physiol 2006, 291:851-859" should be "Am J Physiol Cell Physiol 2006, 291:C851-859"
15. "Balasubramaniem A, Nosratola D, Said HM" should be "Ashokkumar B, Vaziri ND, Said HM." "291:796-805." should be "291:F796-805."

Bibliography update

Armando Reyes-Engel — 2010-03-22T16:33:48Z

We believe this is a very interesting article on a topic of research in which we are involved especially. As it is mentioned in the history of this publication there are very few articles published about this issue (one review and 5 original papers), and should not pose any problem to update the bibliography in this area. I am sending this letter to remark that our team published the first article, about this subject in The Lancet in 1998 whose title must not be overlooked, in any search, since it includes the words Genetic Selection and folate, and a second article in which the design is similar to this one because we refer to distribute the population into four cohorts and that also includes the term of genetic selection with the MTHFR gene polymorphism in the title. No other interest than scientific recognition, without which we would lack professional motivation and economic loss, we send this comment.
Bibliography about Human Genetic Selection and Folate

Genetic selection and folate intake during pregnancy.
Muñoz-Moran E, Dieguez-Lucena JL, Fernandez-Arcas N, Peran-Mesa S, Reyes-Engel A.
Lancet. 1998 Oct 3;352(9134):1120-1. No abstract available. PMID: 9798595 [PubMed - indexed for MEDLINE]Related articles

Implications on human fertility of the 677C-->T and 1298A-->C polymorphisms of the MTHFR gene: consequences of a possible genetic selection.
Reyes-Engel A, Muñoz E, Gaitan MJ, Fabre E, Gallo M, Dieguez JL, Ruiz M, Morell M.
Mol Hum Reprod. 2002 Oct;8(10):952-7.PMID: 12356947 [PubMed - indexed for MEDLINE]Related articlesFree article

Folic acid - vitamin and panacea or genetic time bomb?
Lucock M, Yates Z.
Nat Rev Genet. 2005 Mar;6(3):235-40. Review.PMID: 15738964 [PubMed - indexed for MEDLINE]Related articles

Preliminary evidence for genetic selection of 677T-MTHFR by natural annual cycle of folate abundance.
Lucock M, Yates Z, Ng X, Veysey M, Blades B, Travers C, Lewis P, Sturm J, Roach P.
J Nutrigenet Nutrigenomics. 2008;1(1-2):24-9. Epub 2007 Oct 16.PMID: 19918112 [PubMed - indexed for MEDLINE]Related articles

Folic acid use in pregnancy and embryo selection.
Haggarty P, Campbell DM, Duthie S, Andrews K, Hoad G, Piyathilake C, Fraser I, McNeill G.
BJOG. 2008 Jun;115(7):851-6.PMID: 18485163 [PubMed - indexed for MEDLINE]Related articles

Human genetic selection on the MTHFR 677C>T polymorphism.
Mayor-Olea A, Callejón G, Palomares AR, Jiménez AJ, Gaitán MJ, Rodríguez A, Ruiz M, Reyes-Engel A.
BMC Med Genet. 2008 Nov 28;9:104.PMID: 19040733 [PubMed - indexed for MEDLINE]Related articlesFree article

Reply to : Correct use of the Manchester scoring system

Louise Bordeleau — 2009-05-05T10:28:45Z

We greatly appreciate the feedback provided by Dr. Evans on the correct use of the Manchester scoring system. We have since recalculated the combined scores of the Manchester Model using the correct scoring system. The AUC of the Manchester Model using the updated calculation is 0.73 (0.64-0.79); low risk subset 0.67 (0.50-0.80) and high risk subset 0.75 (0.65-0.83) [Table 4]. At the conventional testing threshold of 15, both the sensitivity and specificity of the Manchester Model are 0.66 [Table 5]. The performance of the Manchester Model is therefore similar to the performances observed with other models used in our analyses including the BRCAPRO, PennII, Myriad II, FHAT and BOADICEA.
The clarification in the use of the model deserves to be noted as it can affect the performance of the model based on the results observed in our study.