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{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
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'''ATP-binding cassette transporter sub-family C member 11''' is a [[protein]] that in humans is encoded by the ''ABCC11'' [[gene]].<ref name="pmid11483364">{{cite journal | vauthors = Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, Schuetz JD, Swoboda KJ, Ptácek LJ, Rosier M, Dean M, Allikmets R | title = Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 | journal = Gene | volume = 273 | issue = 1 | pages = 89–96 | date = Jul 2001 | pmid = 11483364 | pmc = | doi = 10.1016/S0378-1119(01)00572-8 }}</ref><ref name="pmid11435397">{{cite journal | vauthors = Dean M, Rzhetsky A, Allikmets R | title = The human ATP-binding cassette (ABC) transporter superfamily | journal = Genome Research | volume = 11 | issue = 7 | pages = 1156–66 | date = Jul 2001 | pmid = 11435397 | pmc = | doi = 10.1101/gr.184901 }}</ref><ref name="entrez"/>
{{Infobox_gene}}{{Expand German|date=October 2018|topic=sci}}
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'''ATP-binding cassette transporter sub-family C member 11''', also '''MRP8''' (''Multidrug Resistance-Related Protein 8''), is a [[Membrane transport protein|membrane transporter]] that exports certain molecules from inside a cell. It is a [[protein]] that in humans is encoded by [[gene]] ''ABCC11''.<ref name="pmid11483364">{{cite journal | vauthors = Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, Schuetz JD, Swoboda KJ, Ptácek LJ, Rosier M, Dean M, Allikmets R | title = Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 | journal = Gene | volume = 273 | issue = 1 | pages = 89–96 | date = Jul 2001 | pmid = 11483364 | doi = 10.1016/S0378-1119(01)00572-8 }}</ref><ref name="pmid11435397">{{cite journal | vauthors = Dean M, Rzhetsky A, Allikmets R | title = The human ATP-binding cassette (ABC) transporter superfamily | journal = Genome Research | volume = 11 | issue = 7 | pages = 1156–66 | date = Jul 2001 | pmid = 11435397 | doi = 10.1101/gr.184901| s2cid = 9528197 | doi-access = free }}</ref><ref name="entrez"/>


The gene is responsible for determination of human [[Earwax|cerumen]] type (wet or dry ear wax) and presence of underarm [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by excessive [[apocrine]] secretion).
The gene is responsible for determination of human [[Earwax|cerumen]] type (wet or dry ear wax) and presence of underarm [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by [[apocrine]] secretion), and is associated with [[colostrum]] secretion.<ref>{{cite journal |last1=Miura |first1=Kiyonori |last2=Yoshiura |first2=Koh-ichiro |last3=Miura |first3=Shoko |last4=Shimada |first4=Takako |last5=Yamasaki |first5=Kentaro |last6=Yoshida |first6=Atsushi |last7=Nakayama |first7=Daisuke |last8=Shibata |first8=Yoshisada |last9=Niikawa |first9=Norio |last10=Masuzaki |first10=Hideaki |title=A strong association between human earwax-type and apocrine colostrum secretion from the mammary gland |journal=Human Genetics |date=June 2007 |volume=121 |issue=5 |pages=631–633 |doi=10.1007/s00439-007-0356-9 |pmid=17394018 |s2cid=575882 |url=https://pubmed.ncbi.nlm.nih.gov/17394018/ |issn=0340-6717}}</ref>


== Function ==
== Function ==
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The protein encoded by this gene is a member of the superfamily of [[ATP-binding cassette transporter|ATP-binding cassette]] (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The ABCC11 transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a [[single nucleotide polymorphism]] (SNP) in this gene is responsible for determination of human [[earwax]] type and presence of underarm odour. This gene and family member [[ABCC12]] are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=85320}}</ref>

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The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human [[earwax]] type and presence of underarm odour. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=85320| accessdate = }}</ref>


== Molecular genetics ==
== Molecular genetics ==
[[File:ABCC11 genmap 01.svg|left|thumb|Location of ''ABCC11'' with its 30 exons on chromosome 16. The important single nucleotide polymorphism (SNP) 538G → A is located on exon 4.]]
The ''ABCC11'' [[gene]] is present in the [[human genome]] as two [[allele]]s, differing in one [[nucleotide]] also known as a [[Single-nucleotide polymorphism|single nucleotide polymorphism (SNP)]].<ref name="Toyoda_2009">{{cite journal | vauthors = Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, Sakai Y, Ota I, Lezhava A, Hayashizaki Y, Niikawa N, Ishikawa T | title = Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type? | journal = FASEB Journal | volume = 23 | issue = 6 | pages = 2001–13 | date = Jun 2009 | pmid = 19383836 | doi = 10.1096/fj.09-129098 }}</ref> A SNP in the ''ABCC11'' gene on [[Chromosome 16 (human)|chromosome 16]] at [[Nucleobase|base]] position 538 of either a [[guanine]] or [[adenine]] controls for multiple distinct [[phenotype]]s.<ref name="Toyoda_2009" /><ref name="Yoshiura_2006" /> These respectively code for [[glycine]] and [[arginine]] in the gene's [[protein]] product. [[Heredity|Dominant inheritance]] of the GG or GA [[genotype]] is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include [[Earwax|cerumen]] type (wet or dry ear wax), [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by excessive [[apocrine]] secretion), and [[breast cancer]] risk, although there is ongoing debate on whether if there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility.<ref name="Rodriguez_2013">{{cite journal | vauthors = Rodriguez S, Steer CD, Farrow A, Golding J, Day IN | title = Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 7 | pages = 1760–7 | date = Jul 2013 | pmid = 23325016 | pmc = 3674910 | doi = 10.1038/jid.2012.480 }}</ref><ref>{{cite journal | vauthors = Park YJ, Shin MS | title = What is the best method for treating osmidrosis? | journal = Annals of Plastic Surgery | volume = 47 | issue = 3 | pages = 303–9 | date = Sep 2001 | pmid = 11562036 | doi=10.1097/00000637-200109000-00014}}</ref> The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele.<ref name="Rodriguez_2013"/> Note this phenotype requires only the presence of one guanine. The [[homozygous]] recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.<ref name="Rodriguez_2013" />
The ''ABCC11'' [[gene]] is present in the [[human genome]] as two [[allele]]s, differing in one [[nucleotide]] also known as a [[Single-nucleotide polymorphism|single nucleotide polymorphism (SNP)]].<ref name="Toyoda_2009">{{cite journal | vauthors = Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, Sakai Y, Ota I, Lezhava A, Hayashizaki Y, Niikawa N, Ishikawa T | title = Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type? | journal = FASEB Journal | volume = 23 | issue = 6 | pages = 2001–13 | date = Jun 2009 | pmid = 19383836 | doi = 10.1096/fj.09-129098 | doi-access = free | s2cid = 26853548 }}</ref> A SNP in the ''ABCC11'' gene on [[Chromosome 16 (human)|chromosome 16]] at [[Nucleobase|base]] position 538 of either a [[guanine]] or [[adenine]] determines two distinct groups of [[phenotype]]s.<ref name="Toyoda_2009" /><ref name="Yoshiura_2006" /> These respectively code for [[glycine]] and [[arginine]] in the gene's [[protein]] product. [[Heredity|Dominant inheritance]] of the GG or GA [[genotype]] is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include [[Earwax|cerumen]] type (wet or dry ear wax), [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by excessive [[apocrine]] secretion), and possibly [[breast cancer]] risk, although there is ongoing debate on whether there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility.<ref name="Rodriguez_2013">{{cite journal | vauthors = Rodriguez S, Steer CD, Farrow A, Golding J, Day IN | title = Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 7 | pages = 1760–7 | date = Jul 2013 | pmid = 23325016 | pmc = 3674910 | doi = 10.1038/jid.2012.480 }}</ref><ref>{{cite journal | vauthors = Park YJ, Shin MS | title = What is the best method for treating osmidrosis? | journal = Annals of Plastic Surgery | volume = 47 | issue = 3 | pages = 303–9 | date = Sep 2001 | pmid = 11562036 | doi=10.1097/00000637-200109000-00014| s2cid = 25590802 }}</ref> The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele.<ref name="Rodriguez_2013"/> Note this phenotype requires only the presence of one guanine. The [[homozygous]] recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.<ref name="Rodriguez_2013" />


The alleles containing a guanine produce a protein that is [[Glycosylation|glycosylated]] but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by [[proteasome]]s.<ref name="Toyoda_2009"/> This effect is localized to [[ceruminous gland]] membranes.<ref name="Toyoda_2009" /> Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ''ABCC11'' gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.<ref name="Toyoda_2009" />
The alleles containing a guanine produce a protein that is [[Glycosylation|glycosylated]] but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by [[proteasome]]s.<ref name="Toyoda_2009"/> This effect is localized to [[ceruminous gland]] membranes.<ref name="Toyoda_2009" /> Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ''ABCC11'' gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.<ref name="Toyoda_2009" />


From an [[evolution]]ary perspective, the implications of cerumen type on [[Fitness (biology)|fitness]] are unknown although odorless sweat in ancient Northern [[Eurasia]]n populations have been postulated to have an [[Adaptation|adaptive]] advantage for cold weather.<ref name="Yoshiura_2006" /> In some nonhuman [[mammal]]s, [[mating]] signals via release of an odor enhanced by increased apocrine secretion may be a factor in [[sexual selection]].<ref name="Yoshiura_2006" />
From an [[evolution]]ary perspective, the implications of cerumen type on [[Fitness (biology)|fitness]] are unknown. However, odorless sweat in ancient Northern [[Eurasia]]n populations has been postulated to have an [[Adaptation|adaptive]] advantage for cold weather.<ref name="Yoshiura_2006" /> In some nonhuman [[mammal]]s, [[mating]] signals via release of an odor enhanced by increased apocrine secretion may be a factor in [[sexual selection]].<ref name="Yoshiura_2006" />


Physical [[human]] traits that are controlled by a single gene are [[Human genetics#Human traits with simple inheritance patterns|uncommon]]. Most human characteristics are controlled by multiple genes ([[polygene]]s) although ''ABCC11'' is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a [[Pleiotropy|pleiotropic]] gene.
Physical [[human]] traits that are controlled by a single gene are [[Human genetics#Human traits with simple inheritance patterns|uncommon]]. Most human characteristics are controlled by multiple genes ([[polygene]]s); ''ABCC11'' is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a [[Pleiotropy|pleiotropic]] gene.


== Demographics ==
== Demographics ==
[[File:World map ABCC11 A Allele.svg|thumb|170px|World map of the distribution of the A allele of the single nucleotide polymorphism rs17822931 in the ABCC11 gene. The proportion of A alleles in each population is represented by the white area in each circle.]]
The history of the migration of humans can be traced back using the ''ABCC11'' gene alleles. The variation between ear wax and body odor in [[Ethnic group|ethnicities]] around the world are specifically due to the ''ABCC11'' gene alleles.<ref name="Yoshiura_2006" /> It is hypothesized that 40,000 years ago, an ancient [[Mongoloid]] tribe evolved the dry ear wax phenotype that followed a spread of the dry ear wax allele to other regions of Asia via migration of the ancient tribe.<ref name="Ishikawa_2012">{{cite journal | vauthors = Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N | title = Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion | journal = Frontiers in Genetics | volume = 3 | pages = 306 | date = 2012-01-01 | pmid = 23316210 | pmc = 3539816 | doi = 10.3389/fgene.2012.00306 }}</ref> The gene spread as a result of it being a beneficial [[Adaptation|adaption]] or through an evolutionary neutral [[mutation]] mechanism that went through [[genetic drift]] events.<ref name="Ishikawa_2012" />
The history of the migration of humans can be traced back using the ''ABCC11'' gene alleles. The variation between ear wax in [[Ethnic group|ethnicities]] around the world are specifically due to the ''ABCC11'' gene alleles.<ref name="Yoshiura_2006" /> It is believed that the derived allele originated in an ancient [[East Asia]]n population.<ref>{{cite journal |last1=Hori |first1=Yusuke S. |last2=Yamada |first2=Aiko |last3=Matsuda |first3=Norifumi |last4=Ono |first4=Yusuke |last5=Starenki |first5=Dmytro |last6=Sosonkina |first6=Nadiya |last7=Yoshiura |first7=Koh-ichiro |last8=Niikawa |first8=Norio |last9=Ohta |first9=Tohru |title=A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene |journal=Human Biology |date=2017 |volume=89 |issue=4 |pages=305–307 |doi=10.13110/humanbiology.89.4.04 |pmid=30047321 |s2cid=51721105 |url=https://muse.jhu.edu/article/700223 |issn=1534-6617}} "were highest in East Asia, with decreasing frequencies observed toward Europe and Southern Asia, suggesting an East Asian origin."</ref> The gene may have spread as a result of it being a beneficial [[Adaptation|adaption]] or through an evolutionary neutral [[mutation]] mechanism that went through [[genetic drift]] events, or through sexual selection.<ref>{{cite journal | vauthors = Martin A, Saathoff M, Kuhn F, Max H, Terstegen L, Natsch A | title = A functional ABCC11 allele is essential in the biochemical formation of human axillary odor | journal = The Journal of Investigative Dermatology | volume = 130 | issue = 2 | pages = 529–540 | date = February 2010 | pmid = 19710689 | doi = 10.1038/jid.2009.254 | s2cid = 36754463 | doi-access = free }}</ref>


An analysis of [[ancient DNA]] of [[Eastern Hunter Gatherers|Eastern European hunter gatherers]], [[Scandinavian Hunter Gatherers]], [[Western Hunter Gatherers]] and [[Early European Farmers]]. The study found that the derived allele of ABCC11 associated with dry earwax and reduced body odor was absent in all European hunter gatherers, except for a [[Western Hunter Gatherer]] from [[Mesolithic]] central Europe. The derived allele was absent in the paleolithic hunter gatherer [[Kostyonki–Borshchyovo#Human remains|Kostenki 14]], who is deeply related to [[Ancient North Eurasians]].<ref>{{cite journal |last1=Günther |first1=T |last2=Malmström |first2=H |last3=Svensson |first3=EM |title=Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation. |journal=PLOS Biology |date=January 2018 |volume=16 |issue=1 |pages=e2003703 |doi=10.1371/journal.pbio.2003703 |pmid=29315301 |pmc=5760011 |doi-access=free }} From [https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.2003703.s013 Supporting Information file S8], page 17/28: "Furthermore, SF9, SBj, Hum2 and SF12 as well as all other HG tested (with the exception of KO1), carried allelic variants at ABCC1 gene associated with wet earwax, normal body odor and normal
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The frequency of alleles for dry ear wax and odorless sweat is most concentrated in East- and Northeast [[Asia]], most notably [[Korea]], [[China]], [[Mongolia]], and western [[Japan]].<ref name="Yoshiura_2006">{{cite journal | vauthors = Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N | display-authors = 6 | title = A SNP in the ABCC11 gene is the determinant of human earwax type | journal = Nature Genetics | volume = 38 | issue = 3 | pages = 324–30 | date = Mar 2006 | pmid = 16444273 | doi = 10.1038/ng1733 }}</ref> Conversely the frequency of the allele for wet ear wax and odored sweat are highest in [[African Americans|African-American]] and [[Sub-Saharan Africans|sub-saharan]] populations.<ref name="Yoshiura_2006" /> A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and a east-west gradient can also be drawn from eastern Siberia to western Europe.<ref name="Yoshiura_2006" /> The [[Allele frequency|allele frequencies]] within ethnicities continued to be maintained because the ''ABCC11'' gene is inherited as a [[haplotype]], a group of genes or alleles that tend to be inherited as a single unit<ref name="Yoshiura_2006" /><ref>{{cite journal | vauthors = Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, Preti G | title = Ethnic/racial and genetic influences on cerumen odorant profiles | journal = Journal of Chemical Ecology | volume = 41 | issue = 1 | pages = 67–74 | date = Jan 2015 | pmid = 25501636 | pmc = 4304888 | doi = 10.1007/s10886-014-0533-y }}</ref>[[Haplotype|.]]
colostrum [69]." See also: [https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.2003703.s001 Supporting Information File S1]</ref>


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The frequency of alleles for dry ear wax is most concentrated in [[East Asia]]; most notably [[China]], [[Japan]], [[Korea]], and [[Mongolia]]. The allele frequency is highest among the northern [[Han Chinese]] and [[Koreans]]; followed by [[Mongols]], southern Han Chinese, and [[Yamato people|Yamato Japanese]], respectively. The frequency is low among the [[Ryukyuan people|Ryukyuans]] and [[Ainu people|Ainu]].<ref name="Yoshiura_2006">{{cite journal | vauthors = Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N | title = A SNP in the ABCC11 gene is the determinant of human earwax type | journal = Nature Genetics | volume = 38 | issue = 3 | pages = 324–30 | date = Mar 2006 | pmid = 16444273 | doi = 10.1038/ng1733 | s2cid = 3201966 |url = https://www.nature.com/articles/ng1733}}</ref> The derived allele is not rare in [[South Asia]], with 54% of [[Dravidian people]] from [[Tamil Nadu]] carrying an AA genotype.<ref name="Yoshiura_2006" /> A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and an east–west gradient can also be drawn from eastern Siberia to western Europe.<ref name="Yoshiura_2006" /> The [[Allele frequency|allele frequencies]] within ethnicities continued to be maintained because the ''ABCC11'' gene is inherited as a [[haplotype]], a group of genes or alleles that tend to be inherited as a single unit.<ref name="Yoshiura_2006" /><ref>{{cite journal | vauthors = Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, Preti G | title = Ethnic/racial and genetic influences on cerumen odorant profiles | journal = Journal of Chemical Ecology | volume = 41 | issue = 1 | pages = 67–74 | date = Jan 2015 | pmid = 25501636 | pmc = 4304888 | doi = 10.1007/s10886-014-0533-y | bibcode = 2015JCEco..41...67P }}</ref>
The University of Bristol research suggested only 0.006 percent of the Korean population have the ABCC11 gene, a major culprit behind the odor problem. The research was based on the Allel Frequency Database (ALFRED), a gene database designed by Yale University. Researchers said the Korean ratio was the world's lowest.<ref>http://www.koreatimes.co.kr/www/news/world/2016/05/182_205177.html</ref>

The amount of [[volatile organic compound]]s (VOCs) in ear wax was found to be related to variation in ABCC11 [[genotype]], which in turn is dependent on ethnic origin. In particular, the rs17822931 genotype, which is especially prevalent in East Asians, is correlated with lower VOC levels. However, VOC levels were not found to vary significantly qualitatively nor quantitatively for most organic compounds by racial group after [[Bonferroni correction]]s, suggesting that it does not result in ethnic differences.<ref name="pmid26634572">{{cite journal | vauthors = Prokop-Prigge KA, Greene K, Varallo L, Wysocki CJ, Preti G | title = The Effect of Ethnicity on Human Axillary Odorant Production | journal = Journal of Chemical Ecology | volume = 42 | issue = 1 | pages = 33–9 | year = 2016 | pmid = 26634572 | pmc = 4724538 | doi = 10.1007/s10886-015-0657-8 | bibcode = 2016JCEco..42...33P }}</ref>


== See also ==
== See also ==
* [[ATP-binding cassette transporter]]
* [[ATP-binding cassette transporter]]
* [[Body odor]]


== References ==
== References ==
=== Citations ===
{{Reflist|33em}}
{{Reflist}}

=== Sources ===
{{refbegin}}
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* {{NLM content}}
{{refend}}


== Further reading ==
== Further reading ==
{{refbegin|33em}}
{{refbegin|33em}}
* {{cite journal | vauthors = Bera TK, Lee S, Salvatore G, Lee B, Pastan I | title = MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer | journal = Molecular Medicine | volume = 7 | issue = 8 | pages = 509–16 | date = Aug 2001 | pmid = 11591886 | pmc = 1950066 | doi = }}
* {{cite journal | vauthors = Bera TK, Lee S, Salvatore G, Lee B, Pastan I | title = MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer | journal = Molecular Medicine | volume = 7 | issue = 8 | pages = 509–16 | date = Aug 2001 | pmid = 11591886 | pmc = 1950066 | doi = 10.1007/BF03401856}}
* {{cite journal | vauthors = Yabuuchi H, Shimizu H, Takayanagi S, Ishikawa T | title = Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12 | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 933–9 | date = Nov 2001 | pmid = 11688999 | doi = 10.1006/bbrc.2001.5865 }}
* {{cite journal | vauthors = Yabuuchi H, Shimizu H, Takayanagi S, Ishikawa T | title = Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12 | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 933–9 | date = Nov 2001 | pmid = 11688999 | doi = 10.1006/bbrc.2001.5865 }}
* {{cite journal | vauthors = Lai L, Tan TM | title = Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 497–503 | date = Feb 2002 | pmid = 11802779 | pmc = 1222332 | doi = 10.1042/0264-6021:3610497 }}
* {{cite journal | vauthors = Lai L, Tan TM | title = Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 497–503 | date = Feb 2002 | pmid = 11802779 | pmc = 1222332 | doi = 10.1042/0264-6021:3610497 }}
* {{cite journal | vauthors = Stríz I, Jaresová M, Lácha J, Sedlácek J, Vítko S | title = MRP 8/14 and procalcitonin serum levels in organ transplantations | journal = Annals of Transplantation | volume = 6 | issue = 2 | pages = 6–9 | year = 2002 | pmid = 11803621 | doi = }}
* {{cite journal | vauthors = Stríz I, Jaresová M, Lácha J, Sedlácek J, Vítko S | title = MRP 8/14 and procalcitonin serum levels in organ transplantations | journal = Annals of Transplantation | volume = 6 | issue = 2 | pages = 6–9 | year = 2002 | pmid = 11803621 }}
* {{cite journal | vauthors = Tomita H, Yamada K, Ghadami M, Ogura T, Yanai Y, Nakatomi K, Sadamatsu M, Masui A, Kato N, Niikawa N | title = Mapping of the wet/dry earwax locus to the pericentromeric region of chromosome 16 | journal = Lancet | volume = 359 | issue = 9322 | pages = 2000–2 | date = Jun 2002 | pmid = 12076558 | doi = 10.1016/S0140-6736(02)08835-9 }}
* {{cite journal | vauthors = Tomita H, Yamada K, Ghadami M, Ogura T, Yanai Y, Nakatomi K, Sadamatsu M, Masui A, Kato N, Niikawa N | title = Mapping of the wet/dry earwax locus to the pericentromeric region of chromosome 16 | journal = Lancet | volume = 359 | issue = 9322 | pages = 2000–2 | date = Jun 2002 | pmid = 12076558 | doi = 10.1016/S0140-6736(02)08835-9 | s2cid = 20226277 }}
* {{cite journal | vauthors = Turriziani O, Schuetz JD, Focher F, Scagnolari C, Sampath J, Adachi M, Bambacioni F, Riva E, Antonelli G | title = Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11 | journal = The Biochemical Journal | volume = 368 | issue = Pt 1 | pages = 325–32 | date = Nov 2002 | pmid = 12133003 | pmc = 1222956 | doi = 10.1042/BJ20020494 }}
* {{cite journal | vauthors = Turriziani O, Schuetz JD, Focher F, Scagnolari C, Sampath J, Adachi M, Bambacioni F, Riva E, Antonelli G | title = Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11 | journal = The Biochemical Journal | volume = 368 | issue = Pt 1 | pages = 325–32 | date = Nov 2002 | pmid = 12133003 | pmc = 1222956 | doi = 10.1042/BJ20020494 }}
* {{cite journal | vauthors = Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG, Kruh GD | title = MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29509–14 | date = Aug 2003 | pmid = 12764137 | doi = 10.1074/jbc.M304059200 }}
* {{cite journal | vauthors = Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG, Kruh GD | title = MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29509–14 | date = Aug 2003 | pmid = 12764137 | doi = 10.1074/jbc.M304059200 | s2cid = 6081066 | doi-access = free}}
* {{cite journal | vauthors = Bouma G, Lam-Tse WK, Wierenga-Wolf AF, Drexhage HA, Versnel MA | title = Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin | journal = Diabetes | volume = 53 | issue = 8 | pages = 1979–86 | date = Aug 2004 | pmid = 15277376 | doi = 10.2337/diabetes.53.8.1979 }}
* {{cite journal | vauthors = Bouma G, Lam-Tse WK, Wierenga-Wolf AF, Drexhage HA, Versnel MA | title = Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin | journal = Diabetes | volume = 53 | issue = 8 | pages = 1979–86 | date = Aug 2004 | pmid = 15277376 | doi = 10.2337/diabetes.53.8.1979 | doi-access = free | hdl = 1765/10354 | hdl-access = free }}
* {{cite journal | vauthors = Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, Werner S, Sorg C, Roth J | title = MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes | journal = Blood | volume = 104 | issue = 13 | pages = 4260–8 | date = Dec 2004 | pmid = 15331440 | doi = 10.1182/blood-2004-02-0446 }}
* {{cite journal | vauthors = Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, Werner S, Sorg C, Roth J | title = MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes | journal = Blood | volume = 104 | issue = 13 | pages = 4260–8 | date = Dec 2004 | pmid = 15331440 | doi = 10.1182/blood-2004-02-0446 | s2cid = 5407110 | doi-access = free }}
* {{cite journal | vauthors = Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD | title = Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11) | journal = Molecular Pharmacology | volume = 67 | issue = 2 | pages = 545–57 | date = Feb 2005 | pmid = 15537867 | doi = 10.1124/mol.104.007138 }}
* {{cite journal | vauthors = Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD | title = Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11) | journal = Molecular Pharmacology | volume = 67 | issue = 2 | pages = 545–57 | date = Feb 2005 | pmid = 15537867 | doi = 10.1124/mol.104.007138 | s2cid = 18527978 }}
* {{cite journal | vauthors = Bortfeld M, Rius M, König J, Herold-Mende C, Nies AT, Keppler D | title = Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system | journal = Neuroscience | volume = 137 | issue = 4 | pages = 1247–57 | year = 2006 | pmid = 16359813 | doi = 10.1016/j.neuroscience.2005.10.025 }}
* {{cite journal | vauthors = Bortfeld M, Rius M, König J, Herold-Mende C, Nies AT, Keppler D | title = Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system | journal = Neuroscience | volume = 137 | issue = 4 | pages = 1247–57 | year = 2006 | pmid = 16359813 | doi = 10.1016/j.neuroscience.2005.10.025 | s2cid = 22719472 }}
* {{cite journal | vauthors = Viemann D, Barczyk K, Vogl T, Fischer U, Sunderkötter C, Schulze-Osthoff K, Roth J | title = MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program | journal = Blood | volume = 109 | issue = 6 | pages = 2453–60 | date = Mar 2007 | pmid = 17095618 | doi = 10.1182/blood-2006-08-040444 }}
* {{cite journal | vauthors = Viemann D, Barczyk K, Vogl T, Fischer U, Sunderkötter C, Schulze-Osthoff K, Roth J | title = MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program | journal = Blood | volume = 109 | issue = 6 | pages = 2453–60 | date = Mar 2007 | pmid = 17095618 | doi = 10.1182/blood-2006-08-040444 | doi-access = free }}
{{refend}}
{{refend}}


== External links ==
==External links==
{{Commonscat}}
* {{MeshName|ABCC11+protein,+human}}
* {{MeshName|ABCC11+protein,+human}}
* {{UCSC gene info|ABCC11}}
* {{UCSC gene info|ABCC11}}


⚫
{{NLM content}}
{{ABC transporters}}
{{ABC transporters}}


{{DEFAULTSORT:Abcc11}}
{{DEFAULTSORT:Abcc11}}
[[Category:ABC transporters]]
[[Category:ATP-binding cassette transporters]]

Latest revision as of 05:53, 20 September 2024

ABCC11
Identifiers
AliasesABCC11, ATP-binding cassette, sub-family C (CFTR/MRP), member 11, EWWD, MRP8, WW, ATP binding cassette subfamily C member 11, ATP-binding cassette transporter sub-family C member 1
External IDsOMIM: 607040; HomoloGene: 69511; GeneCards: ABCC11; OMA:ABCC11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

85320

n/a

Ensembl

ENSG00000121270

n/a

UniProt

Q96J66

n/a

RefSeq (mRNA)

NM_032583
NM_033151
NM_145186
NM_001370496
NM_001370497

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 16: 48.17 – 48.25 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

ATP-binding cassette transporter sub-family C member 11, also MRP8 (Multidrug Resistance-Related Protein 8), is a membrane transporter that exports certain molecules from inside a cell. It is a protein that in humans is encoded by gene ABCC11.[3][4][5]

The gene is responsible for determination of human cerumen type (wet or dry ear wax) and presence of underarm osmidrosis (odor associated with sweat caused by apocrine secretion), and is associated with colostrum secretion.[6]

Function

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The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The ABCC11 transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a single nucleotide polymorphism (SNP) in this gene is responsible for determination of human earwax type and presence of underarm odour. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.[5]

Molecular genetics

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Location of ABCC11 with its 30 exons on chromosome 16. The important single nucleotide polymorphism (SNP) 538G → A is located on exon 4.

The ABCC11 gene is present in the human genome as two alleles, differing in one nucleotide also known as a single nucleotide polymorphism (SNP).[7] A SNP in the ABCC11 gene on chromosome 16 at base position 538 of either a guanine or adenine determines two distinct groups of phenotypes.[7][8] These respectively code for glycine and arginine in the gene's protein product. Dominant inheritance of the GG or GA genotype is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include cerumen type (wet or dry ear wax), osmidrosis (odor associated with sweat caused by excessive apocrine secretion), and possibly breast cancer risk, although there is ongoing debate on whether there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility.[9][10] The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele.[9] Note this phenotype requires only the presence of one guanine. The homozygous recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.[9]

The alleles containing a guanine produce a protein that is glycosylated but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by proteasomes.[7] This effect is localized to ceruminous gland membranes.[7] Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ABCC11 gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.[7]

From an evolutionary perspective, the implications of cerumen type on fitness are unknown. However, odorless sweat in ancient Northern Eurasian populations has been postulated to have an adaptive advantage for cold weather.[8] In some nonhuman mammals, mating signals via release of an odor enhanced by increased apocrine secretion may be a factor in sexual selection.[8]

Physical human traits that are controlled by a single gene are uncommon. Most human characteristics are controlled by multiple genes (polygenes); ABCC11 is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a pleiotropic gene.

Demographics

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World map of the distribution of the A allele of the single nucleotide polymorphism rs17822931 in the ABCC11 gene. The proportion of A alleles in each population is represented by the white area in each circle.

The history of the migration of humans can be traced back using the ABCC11 gene alleles. The variation between ear wax in ethnicities around the world are specifically due to the ABCC11 gene alleles.[8] It is believed that the derived allele originated in an ancient East Asian population.[11] The gene may have spread as a result of it being a beneficial adaption or through an evolutionary neutral mutation mechanism that went through genetic drift events, or through sexual selection.[12]

An analysis of ancient DNA of Eastern European hunter gatherers, Scandinavian Hunter Gatherers, Western Hunter Gatherers and Early European Farmers. The study found that the derived allele of ABCC11 associated with dry earwax and reduced body odor was absent in all European hunter gatherers, except for a Western Hunter Gatherer from Mesolithic central Europe. The derived allele was absent in the paleolithic hunter gatherer Kostenki 14, who is deeply related to Ancient North Eurasians.[13]

The frequency of alleles for dry ear wax is most concentrated in East Asia; most notably China, Japan, Korea, and Mongolia. The allele frequency is highest among the northern Han Chinese and Koreans; followed by Mongols, southern Han Chinese, and Yamato Japanese, respectively. The frequency is low among the Ryukyuans and Ainu.[8] The derived allele is not rare in South Asia, with 54% of Dravidian people from Tamil Nadu carrying an AA genotype.[8] A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and an east–west gradient can also be drawn from eastern Siberia to western Europe.[8] The allele frequencies within ethnicities continued to be maintained because the ABCC11 gene is inherited as a haplotype, a group of genes or alleles that tend to be inherited as a single unit.[8][14]

The amount of volatile organic compounds (VOCs) in ear wax was found to be related to variation in ABCC11 genotype, which in turn is dependent on ethnic origin. In particular, the rs17822931 genotype, which is especially prevalent in East Asians, is correlated with lower VOC levels. However, VOC levels were not found to vary significantly qualitatively nor quantitatively for most organic compounds by racial group after Bonferroni corrections, suggesting that it does not result in ethnic differences.[15]

See also

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References

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Citations

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121270 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, et al. (Jul 2001). "Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12". Gene. 273 (1): 89–96. doi:10.1016/S0378-1119(01)00572-8. PMID 11483364.
  4. ^ Dean M, Rzhetsky A, Allikmets R (Jul 2001). "The human ATP-binding cassette (ABC) transporter superfamily". Genome Research. 11 (7): 1156–66. doi:10.1101/gr.184901. PMID 11435397. S2CID 9528197.
  5. ^ a b "Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11".
  6. ^ Miura K, Yoshiura Ki, Miura S, Shimada T, Yamasaki K, Yoshida A, et al. (June 2007). "A strong association between human earwax-type and apocrine colostrum secretion from the mammary gland". Human Genetics. 121 (5): 631–633. doi:10.1007/s00439-007-0356-9. ISSN 0340-6717. PMID 17394018. S2CID 575882.
  7. ^ a b c d e Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, et al. (Jun 2009). "Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?". FASEB Journal. 23 (6): 2001–13. doi:10.1096/fj.09-129098. PMID 19383836. S2CID 26853548.
  8. ^ a b c d e f g h Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, et al. (Mar 2006). "A SNP in the ABCC11 gene is the determinant of human earwax type". Nature Genetics. 38 (3): 324–30. doi:10.1038/ng1733. PMID 16444273. S2CID 3201966.
  9. ^ a b c Rodriguez S, Steer CD, Farrow A, Golding J, Day IN (Jul 2013). "Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene". The Journal of Investigative Dermatology. 133 (7): 1760–7. doi:10.1038/jid.2012.480. PMC 3674910. PMID 23325016.
  10. ^ Park YJ, Shin MS (Sep 2001). "What is the best method for treating osmidrosis?". Annals of Plastic Surgery. 47 (3): 303–9. doi:10.1097/00000637-200109000-00014. PMID 11562036. S2CID 25590802.
  11. ^ Hori YS, Yamada A, Matsuda N, Ono Y, Starenki D, Sosonkina N, et al. (2017). "A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene". Human Biology. 89 (4): 305–307. doi:10.13110/humanbiology.89.4.04. ISSN 1534-6617. PMID 30047321. S2CID 51721105. "were highest in East Asia, with decreasing frequencies observed toward Europe and Southern Asia, suggesting an East Asian origin."
  12. ^ Martin A, Saathoff M, Kuhn F, Max H, Terstegen L, Natsch A (February 2010). "A functional ABCC11 allele is essential in the biochemical formation of human axillary odor". The Journal of Investigative Dermatology. 130 (2): 529–540. doi:10.1038/jid.2009.254. PMID 19710689. S2CID 36754463.
  13. ^ Günther T, Malmström H, Svensson EM (January 2018). "Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation". PLOS Biology. 16 (1): e2003703. doi:10.1371/journal.pbio.2003703. PMC 5760011. PMID 29315301. From Supporting Information file S8, page 17/28: "Furthermore, SF9, SBj, Hum2 and SF12 as well as all other HG tested (with the exception of KO1), carried allelic variants at ABCC1 gene associated with wet earwax, normal body odor and normal colostrum [69]." See also: Supporting Information File S1
  14. ^ Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, et al. (Jan 2015). "Ethnic/racial and genetic influences on cerumen odorant profiles". Journal of Chemical Ecology. 41 (1): 67–74. Bibcode:2015JCEco..41...67P. doi:10.1007/s10886-014-0533-y. PMC 4304888. PMID 25501636.
  15. ^ Prokop-Prigge KA, Greene K, Varallo L, Wysocki CJ, Preti G (2016). "The Effect of Ethnicity on Human Axillary Odorant Production". Journal of Chemical Ecology. 42 (1): 33–9. Bibcode:2016JCEco..42...33P. doi:10.1007/s10886-015-0657-8. PMC 4724538. PMID 26634572.

Sources

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Further reading

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