Haplogroup O-K18

Haplogroup O-K18
Ancestor	O-P31
Descendants	O-M95, O-M88, O-M297
Defining mutations	K18, F1888/M1356, M1307/K19, CTS279/M1282, plus 60 other SNPs

In genetics, Haplogroup O-K18 is a human Y-chromosome DNA haplogroup. Haplogroup O-K18 is a descendant branch of Haplogroup O-P31.

Distribution

Haplogroup O-K18 is distributed widely in Asia, from southern India to the Altai Mountains and Central Asia in the west, and from Indonesia to northern China and Japan in the east. It is found only at marginally low frequencies of approximately 1% at the periphery of its distribution in southern India, Central Asia, northern China, and Japan, but many populations within the vast intervening territory in South Asia, Southeast Asia, and southern China display a greatly elevated frequency of Haplogroup O-K18 Y-chromosomes. Patrilines within the O-M95 subclade of Haplogroup O-K18 predominate among the Austroasiatic-speaking populations of South and Southeast Asia, such as the Khmer of Cambodia and the Khasi of Meghalaya in northeastern India. Some researchers have reported that slightly over half of all men in a composite sample of Austroasiatic speakers belonged to Haplogroup O-M95. Haplogroup O-M122, which attains its peak frequency among the Sino-Tibetan and Hmong–Mien peoples of China and Southeast Asia, and Haplogroup O-M119, which predominates among Taiwanese aborigines and many populations of the Philippines, also generally occur among speakers of Austroasiatic languages in South China and the Indochinese Peninsula, but usually at much lower frequencies than Haplogroup O-M95. The hypothesis that Haplogroup O-M95 was the major Y-chromosome haplogroup of the proto-Austroasiatic population is strengthened by the fact that Haplogroup O-M95 is the only haplogroup found among many Austroasiatic-speaking tribes, such as the Mlabri people of Thailand, Mang people of southern China and northern Vietnam, Juang of mainland India, and the Nicobarese and Shompen of the Nicobar Islands (Sahoo 2006 and Trivedi 2006).

Haplogroup O-M95 also has been observed with high frequency in samples of Tai–Kadai-speaking peoples of Thailand and neighboring areas, which may reflect assimilation of the older Austroasiatic Mon–Khmer populations that have left ample evidence of their presence in the region prior to the immigration of Tai–Kadai speakers.

Outside of the region in which Austroasiatic languages are currently spoken or have a historically attested presence, Haplogroup O-M95 reaches its highest frequencies among the populations of the islands of Sumatra, Java, Bali, and Borneo in western and central Indonesia (Underhill 2001). Haplogroup O-M95 has been found to be by far the most common Y-chromosome haplogroup among the Balinese, occurring in approximately 58.6% (323/551) of a sample of Balinese men; Haplogroup O-M119 and Haplogroup O-M122, which are typical of Austronesian peoples outside of Malaysia and Indonesia, were observed in only 18.1% (100/551) and 6.9% (38/551) of Balinese men (Karafet 2005). Haplogroup O-M95 has also been found to be the most frequently occurring haplogroup among Malay men in Singapore (Yong 2006). The reason for its substantial presence in these populations, all of which are Austronesian-speaking, is yet to be elucidated.

Subclade distribution

• O-PK4 This lineage has been relocated upstream of M95 following a paper published on the subject in 2011.(Shi Yan et al. 2011) Found in three samples of Han Chinese: 3/65 = 4.6% South China, 1/129 = 0.8% North China, 1/167 = 0.6% East China.
  • O-M95 This lineage is considered typical of Austroasiatic peoples, Tai peoples, Malays, Indonesians, Japanese and Malagasy, with a moderate distribution throughout South Asia, Southeast Asia, East Asia, Central Asia, and Han Chinese.
    • O-M88 This lineage is frequently found among Hani, She people, Vietnamese with a moderate distribution among Tai peoples, Cambodians, Qiang, Hlai, Miao, Yao, Taiwanese aborigines, populations of Borneo (Hurles 2005), Han Chinese of Sichuan, Guangxi, and Guangdong, and Pashtuns (Khaliq 2006)
    • O-M297 More research is needed on this lineage. It is claimed to be downstream from M95 and parallel to M88.

Phylogenetics

Phylogenetic history

Prior to 2002, there were in academic literature at least seven naming systems for the Y-Chromosome Phylogenetic tree. This led to considerable confusion. In 2002, the major research groups came together and formed the Y-Chromosome Consortium (YCC). They published a joint paper that created a single new tree that all agreed to use. Later, a group of citizen scientists with an interest in population genetics and genetic genealogy formed a working group to create an amateur tree aiming at being above all timely. The table below brings together all of these works at the point of the landmark 2002 YCC Tree. This allows a researcher reviewing older published literature to quickly move between nomenclatures.

YCC 2002/2008 (Shorthand)	(α)	(β)	(γ)	(δ)	(ε)	(ζ)	(η)	YCC 2002 (Longhand)	YCC 2005 (Longhand)	YCC 2008 (Longhand)	YCC 2010r (Longhand)	ISOGG 2006	ISOGG 2007	ISOGG 2008	ISOGG 2009	ISOGG 2010	ISOGG 2011	ISOGG 2012
O-M175	26	VII	1U	28	Eu16	H9	I	O*	O	O	O	O	O	O	O	O	O	O
O-M119	26	VII	1U	32	Eu16	H9	H	O1*	O1a	O1a	O1a	O1a	O1a	O1a	O1a	O1a	O1a	O1a
O-M101	26	VII	1U	32	Eu16	H9	H	O1a	O1a1	O1a1a	O1a1a	O1a1	O1a1	O1a1a	O1a1a	O1a1a	O1a1a	O1a1a
O-M50	26	VII	1U	32	Eu16	H10	H	O1b	O1a2	O1a2	O1a2	O1a2	O1a2	O1a2	O1a2	O1a2	O1a2	O1a2
O-P31	26	VII	1U	33	Eu16	H5	I	O2*	O2	O2	O2	O2	O2	O2	O2	O2	O2	O2
O-M95	26	VII	1U	34	Eu16	H11	G	O2a*	O2a	O2a	O2a	O2a	O2a	O2a	O2a	O2a	O2a1	O2a1
O-M88	26	VII	1U	34	Eu16	H12	G	O2a1	O2a1	O2a1	O2a1	O2a1	O2a1	O2a1	O2a1	O2a1	O2a1a	O2a1a
O-SRY465	20	VII	1U	35	Eu16	H5	I	O2b*	O2b	O2b	O2b	O2b	O2b	O2b	O2b	O2b	O2b	O2b
O-47z	5	VII	1U	26	Eu16	H5	I	O2b1	O2b1a	O2b1	O2b1	O2b1a	O2b1a	O2b1	O2b1	O2b1	O2b1	O2b1
O-M122	26	VII	1U	29	Eu16	H6	L	O3*	O3	O3	O3	O3	O3	O3	O3	O3	O3	O3
O-M121	26	VII	1U	29	Eu16	H6	L	O3a	O3a	O3a1	O3a1	O3a1	O3a1	O3a1	O3a1	O3a1	O3a1a	O3a1a
O-M164	26	VII	1U	29	Eu16	H6	L	O3b	O3b	O3a2	O3a2	O3a2	O3a2	O3a2	O3a2	O3a2	O3a1b	O3a1b
O-M159	13	VII	1U	31	Eu16	H6	L	O3c	O3c	O3a3a	O3a3a	O3a3	O3a3	O3a3a	O3a3a	O3a3a	O3a3a	O3a3a
O-M7	26	VII	1U	29	Eu16	H7	L	O3d*	O3c	O3a3b	O3a3b	O3a4	O3a4	O3a3b	O3a3b	O3a3b	O3a2b	O3a2b
O-M113	26	VII	1U	29	Eu16	H7	L	O3d1	O3c1	O3a3b1	O3a3b1	-	O3a4a	O3a3b1	O3a3b1	O3a3b1	O3a2b1	O3a2b1
O-M134	26	VII	1U	30	Eu16	H8	L	O3e*	O3d	O3a3c	O3a3c	O3a5	O3a5	O3a3c	O3a3c	O3a3c	O3a2c1	O3a2c1
O-M117	26	VII	1U	30	Eu16	H8	L	O3e1*	O3d1	O3a3c1	O3a3c1	O3a5a	O3a5a	O3a3c1	O3a3c1	O3a3c1	O3a2c1a	O3a2c1a
O-M162	26	VII	1U	30	Eu16	H8	L	O3e1a	O3d1a	O3a3c1a	O3a3c1a	O3a5a1	O3a5a1	O3a3c1a	O3a3c1a	O3a3c1a	O3a2c1a1	O3a2c1a1

Research publications

The following research teams per their publications were represented in the creation of the YCC Tree.

• α Jobling and Tyler-Smith 2000 and Kaladjieva 2001
• β Underhill 2000
• γ Hammer 2001
• δ Karafet 2001
• ε Semino 2000
• ζ Su 1999
• η Capelli 2001

Phylogenetic trees

This phylogenetic tree of haplogroup O subclades is based on the YCC 2008 tree (Karafet 2008) and subsequent published research.

• O-M95 (M95)
  • O-M88 (M88, M111)

Table of frequencies of O-M95(xM88/M111)

Population	Frequency	Count	Source	SNPs
Nicobarese	1.00	11	Kumar 2007	M95(xM88)
Juang	0.980	49	Kumar 2007	M95(xM88)
Lamet	0.857	35	Cai 2011	M95(xM88)
Korku	0.814	59	Kumar 2007	M95(xM88)
Inh	0.794	34	Cai 2011	M95(xM88)
Katu	0.689	45	Cai 2011	M95(xM88)
Mal	0.660	50	Cai 2011	M95(xM88)
Ho	0.658	79	Kumar 2007	M95(xM88)
Bo	0.643	28	Cai 2011	M95(xM88)
Talieng	0.629	35	Cai 2011	M95(xM88)
Brau	0.625	32	Cai 2011	M95(xM88)
Khmu	0.608	51	Cai 2011	M95(xM88)
Oy	0.600	50	Cai 2011	M95(xM88)
Korwa	0.595	42	Kumar 2007	M95(xM88)
Li (Hlai)	0.588	34	Xue 2006	M95(xM88)
Balinese	0.573	641	Karafet 2010	M95(xM111)
Alak	0.567	30	Cai 2011	M95(xM88)
Suy	0.564	39	Cai 2011	M95(xM88)
Bit	0.536	28	Cai 2011	M95(xM88)
Aheu	0.526	38	Cai 2011	M95(xM88)
Bugan	0.500	32	Cai 2011	M95(xM88)
Java (mostly sampled in Dieng)	0.492	61	Karafet 2010	M95(xM111)
Ngeq	0.486	35	Cai 2011	M95(xM88)
Jeh	0.469	32	Cai 2011	M95(xM88)
Santhal	0.468	109	Kumar 2007	M95(xM88)
Munda	0.453	53	Kumar 2007	M95(xM88)
Laven	0.420	50	Cai 2011	M95(xM88)
So	0.420	50	Cai 2011	M95(xM88)
Muong	0.417	12	Cai 2011	M95(xM88)
Khasi	0.413	92	Kumar 2007	M95(xM88)
Kharia	0.389	36	Kumar 2007	M95(xM88)
Buyi	0.371	35	Xue 2006	M95(xM88)
Lao (Luang Prabang, Laos)	0.360	25	He 2012	M95(xM88)
Kinh	0.333	15	Cai 2011	M95(xM88)
Oraon	0.319	91	Kumar 2007	M95(xM88)
Banjarmasin, Indonesia	0.318	22	Hurles 2005	M95(xM88)
Malaysia	0.313	32	Karafet 2010	M95(xM111)
Mountain Kimmun	0.313	32	Cai 2011	M95(xM88)
Blang	0.308	52	Cai 2011	M95(xM88)
Miao (Yunnan)	0.306	49	Cai 2011	M95(xM88)
Cham (Binh Thuan, Vietnam)	0.305	59	He 2012	M95(xM88)
Lowland Kimmun	0.244	41	Cai 2011	M95(xM88)
Zhuang	0.235	166	Chen 2006	M95(xM111)
Palyu	0.233	30	Cai 2011	M95(xM88)
Kota Kinabalu, Malaysia	0.215	65	Hurles 2005	M95(xM88)
Northern Mien	0.212	33	Cai 2011	M95(xM88)
Flower-head Mien	0.211	19	Cai 2011	M95(xM88)
Borneo (Indonesia)	0.209	86	Karafet 2010	M95(xM111)
Southern Mien	0.194	31	Cai 2011	M95(xM88)
Garo	0.182	33	Kumar 2007	M95(xM88)
Blue Kimmun	0.179	28	Cai 2011	M95(xM88)
Thai (Northern Thailand)	0.176	17	He 2012	M95(xM88)
Xinhmul	0.172	29	Cai 2011	M95(xM88)
Malagasy	0.171	35	Hurles 2005	M95(xM88)
Miao (Guizhou)	0.163	49	Cai 2011	M95(xM88)
Lowland Yao	0.161	31	Cai 2011	M95(xM88)
Batak Toba (Sumatra)	0.158	38	Karafet 2010	M95(xM111)
Daur	0.154	39	Xue 2006	M95(xM88)
Western Mien	0.149	47	Cai 2011	M95(xM88)
Mandar (Sulawesi)	0.130	54	Karafet 2010	M95(xM111)
Pahng	0.129	31	Cai 2011	M95(xM88)
Kinh (Hanoi, Vietnam)	0.118	76	He 2012	M95(xM88)
Kataang	0.108	37	Cai 2011	M95(xM88)
Han (South China)	0.092	65	Yan 2011	PK4(xM88)
Qiang	0.091	33	Xue 2006	M95(xM88)
Top Board Mien	0.091	11	Cai 2011	M95(xM88)
Thin Board Mien	0.091	11	Cai 2011	M95(xM88)
Miao (Hunan)	0.090	100	Cai 2011	M95(xM88)
She	0.088	34	Xue 2006	M95(xM88)
Native Mien	0.073	41	Cai 2011	M95(xM88)
Vietnamese	0.071	70	Karafet 2010	M95(xM111)
Han Chinese (China)	0.061	165	Karafet 2010	M95(xM111)
Hmong Daw (Laos)	0.059	51	Cai 2011	M95(xM88)
Hani	0.059	34	Xue 2006	M95(xM88)
Yao (Liannan, Guangdong)	0.057	35	Xue 2006	M95(xM88)
Bunu	0.056	36	Cai 2011	M95(xM88)
Kapingamarangi	0.048	21	Hurles 2005	M95(xM88)
Flores	0.046	394	Karafet 2010	M95(xM111)
Japanese	0.043	47	Xue 2006	M95(xM88)
Western Samoa	0.040	25	Hurles 2005	M95(xM88)
Ewenki (China)	0.038	26	Xue 2006	M95(xM88)
Northern She (Zhejiang)	0.036	56	Cai 2011	M95(xM88)
Miao (China)	0.034	58	Karafet 2010	M95(xM111)
Han (Lanzhou, Gansu)	0.033	30	Xue 2006	M95(xM88)
Han (Yili, Xinjiang)	0.031	32	Xue 2006	M95(x88)
Han (North China)	0.031	129	Yan 2011	PK4(xM88)
Han (Chengdu, Sichuan)	0.029	34	Xue 2006	M95(xM88)
Han (East China)	0.024	167	Yan 2011	PK4(xM88)
Japanese	0.024	210	Hammer 2006	M95(xM111)
Philippines	0.021	48	Karafet 2010	M95(xM111)
Yao (China)	0.017	60	Karafet 2010	M95(xM111)
Sumba	0.003	350	Karafet 2010	M95(xM111)

Table of frequencies of O-M88/M111

Population	Frequency	Count	Source	SNPs
Xinhmul	0.690	29	Cai 2011	M88
Hani	0.441	34	Xue 2006	M88
She	0.353	51	Karafet 2010	M111
Suy	0.308	39	Cai 2011	M88
Kinh (Hanoi, Vietnam)	0.303	76	He 2012	M88
Lowland Yao	0.290	31	Cai 2011	M88
Kataang	0.270	37	Cai 2011	M88
Zaomin	0.216	37	Cai 2011	M88
Vietnamese	0.200	70	Karafet 2010	M111
Buyi	0.171	35	Xue 2006	M88
Lao (Luang Prabang, Laos)	0.120	25	He 2012	M88
Han (Chengdu, Sichuan)	0.118	34	Xue 2006	M88
Cham (Binh Thuan, Vietnam)	0.085	59	He 2012	M88
Zhuang	0.072	166	Chen 2006	M111
Miao (China)	0.069	58	Karafet 2010	M111
Thai (Northern Thailand)	0.059	17	He 2012	M88
Han (China)	0.055	165	Karafet 2010	M111
Taiwanese aborigines	0.051	39	Hurles 2005	M88
Banjarmasin, Indonesia	0.045	22	Hurles 2005	M88
Pathans (Dir, Pakistan)	0.042	96	Firasat 2007	M88, M111
Malaysia	0.031	32	Karafet 2010	M111
Kota Kinabalu, Malaysia	0.031	65	Hurles 2005	M88
Qiang	0.030	33	Xue 2006	M88
Li (Hlai)	0.029	34	Xue 2006	M88
Yao (Liannan, Guangdong)	0.029	35	Xue 2006	M88
Philippines	0.021	48	Karafet 2010	M111
Taiwanese aborigines	0.021	48	Karafet 2010	M111
Yao (China)	0.017	60	Karafet 2010	M111

See also

Genetics

• genetic genealogy
• Haplogroup
• Haplotype
• Human Y-chromosome DNA haplogroup
• molecular phylogeny
• Paragroup
• Subclade
• Y-chromosome haplogroups by populations
• Y-DNA haplogroups by ethnic groups
• Y-DNA haplogroups by populations of East and Southeast Asia

Y-DNA O subclades

• O-47z
• O-M101
• O-M113
• O-M117
• O-M119
• O-M121
• O-M122
• O-M134
• O-M159
• O-M162
• O-M164
• O-M175
• O-M176
• O-M50
• O-M7
• O-M88
• O-M95
• O-MSY2.2
• O-P31

Y-DNA backbone tree

Evolutionary tree of human Y-chromosome DNA haplogroups [χ 1][χ 2]
	"Y-chromosomal Adam"
		A00	A0-T [χ 3]
			A0	A1[χ 4]
				A1a	A1b
					A1b1		BT
						B	CT
							DE						CF
						D	E		C		F
															F1	F2		F3	GHIJK
																				G	HIJK
																						H	IJK
																							IJ	K
																						I	J		LT [χ 5]		K2
																										L	T		NO [χ 6]	K2b [χ 7]	K2c	K2d		K2e [χ 8]
																													N	O		K2b1 [χ 9]	P
																																	M	S [χ 10]		Q	R
Y-DNA by populations Famous Y-DNA haplotypes
Van Oven M, Van Geystelen A, Kayser M, Decorte R, Larmuseau HD (2014). "Seeing the wood for the trees: a minimal reference phylogeny for the human Y chromosome". Human Mutation 35 (2): 187–91. doi:10.1002/humu.22468. PMID 24166809. International Society of Genetic Genealogy (ISOGG; 2015), Y-DNA Haplogroup Tree 2015. (Access date: 1 February 2015.) Haplogroup A0-T is also known as A0'1'2'3'4. Haplogroup A1 is also known as A1'2'3'4. Haplogroup LT (L298/P326) is also known as Haplogroup K1. Haplogroup NO (M214) is also known as Haplogroup K2a (although the present Haplogroup K2e was also previously known as "K2a"). Haplogroup K2b (M1221/P331/PF5911) is also known as Haplogroup MPS. Haplogroup K2e (K-M147) was previously known as "Haplogroup X" and "K2a" (but is a sibling subclade of the present K2a, also known as Haplogroup NO). Haplogroup K2b1 (P397/P399) is similar to the former Haplogroup MS, but has a broader and more complex internal structure. Haplogroup S (S-M230) was previously known as Haplogroup K5.

References

Footnotes

Works cited

Books

• Underhill, Peter (2005). "Chapter 17: A synopsis of extant Y chromosome diversity in East Asia and Oceania". In Sagart, Laurent; Blench, Roger; Sanchez-Mazas, Alicia. The Peopling of East Asia: Putting Together Archaeology, Linguistics and Genetics. Psychology Press. pp. 297–314. ISBN 9780415322423.

Conference Posters

• Yong, R.Y.Y.; Gan, L.S.H.; Khripin, Y.; Yap, V.B.; Yap, E.P.H. (2006). Workshop 6 Genomic Variation and Diversity: Association of Y chromosome variation with paternal ancestry origin of three ethnic populations in Singapore. HUGO's 11th Human Genome Meeting Helsinki Fair Centre, Helsinki, Finland, Wed 31 May to Sat 3 June 2006. Helsinki, Finland.

Journals

• Firasat, Sadaf; Khaliq, Shagufta; Mohyuddin, Aisha; Papaioannou, Myrto; Tyler-Smith, Chris; Underhill, Peter A; Ayub, Qasim (2006). "Y-chromosomal evidence for a limited Greek contribution to the Pathan population of Pakistan". European Journal of Human Genetics 15 (1): 121–6. doi:10.1038/sj.ejhg.5201726. PMC 2588664. PMID 17047675.
• Fornarino, Simona; Pala, Maria; Battaglia, Vincenza; Maranta, Ramona; Achilli, Alessandro; Modiano, Guido; Torroni, Antonio; Semino, Ornella; Santachiara-Benerecetti, Silvana A (2009). "Mitochondrial and Y-chromosome diversity of the Tharus (Nepal): A reservoir of genetic variation". BMC Evolutionary Biology 9 (1): 154. doi:10.1186/1471-2148-9-154. PMC 2720951. PMID 19573232.
• Hurles, M; Sykes, B; Jobling, M; Forster, P (2005). "The Dual Origin of the Malagasy in Island Southeast Asia and East Africa: Evidence from Maternal and Paternal Lineages". The American Journal of Human Genetics 76 (5): 894–901. doi:10.1086/430051. PMC 1199379. PMID 15793703.
• Karafet, Tatiana M.; Lansing, J. S.; Redd, Alan J.; Watkins, Joseph C.; Surata, S. P. K.; Arthawiguna, W. A.; Mayer, Laura; Bamshad, Michael; et al. (2005). "Balinese Y-Chromosome Perspective on the Peopling of Indonesia: Genetic Contributions from Pre-Neolithic Hunter-Gatherers, Austronesian Farmers, and Indian Traders". Human Biology 77 (1): 93–114. doi:10.1353/hub.2005.0030. PMID 16114819.
• Sahoo, Sanghamitra; Kashyap, V.K. (2006). "Phylogeography of mitochondrial DNA and Y-Chromosome haplogroups reveal asymmetric gene flow in populations of Eastern India". American Journal of Physical Anthropology 131 (1): 84–97. doi:10.1002/ajpa.20399. PMID 16485297.
• Trivedi, Rajni; Sitalaximi, T.; Banerjee, Jheelam; Singh, Anamika; Sircar, P. K.; Kashyap, V. K. (2006). "Molecular insights into the origins of the Shompen, a declining population of the Nicobar archipelago". Journal of Human Genetics 51 (3): 217–26. doi:10.1007/s10038-005-0349-2. PMID 16453062.
• Shi Yan; Chuan-Chao Wang; Hui Li; Shi-Lin Li; Li Jin; The Genographic Consortium (2011). "An updated tree of Y-chromosome Haplogroup O and revised phylogenetic positions of mutations P164 and PK4". European Journal of Human Genetics 19 (9): 1013–1015. doi:10.1038/ejhg.2011.64. PMC 3179364. PMID 21505448.

Further reading

• Hammer, Michael F.; Karafet, Tatiana M.; Park, Hwayong; Omoto, Keiichi; Harihara, Shinji; Stoneking, Mark; Horai, Satoshi (2005). "Dual origins of the Japanese: Common ground for hunter-gatherer and farmer Y chromosomes" (PDF). Journal of Human Genetics 51 (1): 47–58. doi:10.1007/s10038-005-0322-0. PMID 16328082.
• Shi, Hong; Dong, Yong-li; Wen, Bo; Xiao, Chun-Jie; Underhill, Peter A.; Shen, Pei-Dong; Chakraborty, Ranajit; Jin, Li; Su, Bing (2005). "Y-Chromosome Evidence of Southern Origin of the East Asian–Specific Haplogroup O3-M122". The American Journal of Human Genetics 77 (3): 408–19. doi:10.1086/444436. PMC 1226206. PMID 16080116.
• Thanseem, Ismail; Thangaraj, Kumarasamy; Chaubey, Gyaneshwer; Singh, Vijay; Bhaskar, Lakkakula VKS; Reddy, B Mohan; Reddy, Alla G; Singh, Lalji (2006). "Genetic affinities among the lower castes and tribal groups of India: Inference from Y chromosome and mitochondrial DNA". BMC Genetics 7 (1): 42. doi:10.1186/1471-2156-7-42. PMC 1569435. PMID 16893451.