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apophis99942
10-15-2012, 06:36 PM
The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst) and two metrics of haplotype diversity: the integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozygosity (XP-EHH), identified genomic regions and single nucleotide polymorphisms (SNPs) as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK). The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1), known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase) and MCM6 (Minichromosome Maintenance Complex Component) involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit), which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (~58%). The Cytochrome P450 Family 3 Subfamily A (CYP3A) cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated with lactase persistence and cholesterol regulation.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044751
http://forwhattheywereweare.blogspot.com/2012/09/the-maasai-rich-ancestry-lactase.html

Ezana
10-16-2012, 11:08 PM
Interesting. I wonder how many different mutations resulting in lactase persistence they've found in total.

Jean M
03-06-2013, 10:57 AM
Interesting. I wonder how many different mutations resulting in lactase persistence they've found in total.

There have been at least six separate mutations which cause the lactase switch-off to fail.


22018A or rs182549(C): first recognized in Finns. Generally found with 13910T in Europeans, but can appear as an independent cause of lactase persistence in Pakistanis and in the Kazakhs of Northern China.
13907G: East Africa
13910T or rs4988235(A): The dominant mutation in Western Eurasia and South Asia. In South Asia it decreases southward and eastward from a peak in the North-west. Also appears in Central Asia at lower levels: 30% for Kazakhs and 19% for Tajiko-Uzbeks.
13913C: Cameroon, Sudan, Ethiopia, and the Bedouin population in Saudi Arabia.
13915G and 3712C (compound allele): Saudis and East Africans
14010C: East Africa


The paper above refers to GC-14010, which = 14010C.

DMXX
03-06-2013, 11:53 AM
There have been at least six separate mutations which cause the lactase switch-off to fail.


22018A or rs182549(C): first recognized in Finns. Generally found with 13910T in Europeans, but can appear as an independent cause of lactase persistence in Pakistanis and in the Kazakhs of Northern China.



Ah! I finally have genotype proof of my lactose tolerance! I'm CC on rs182549. I do not have 13910T, so my lactose tolerance is of the same "Asiatic" type as Pakistanis and Kazakhs.

newtoboard
03-06-2013, 01:25 PM
Ah! I finally have genotype proof of my lactose tolerance! I'm CC on rs182549. I do not have 13910T, so my lactose tolerance is of the same "Asiatic" type as Pakistanis and Kazakhs.


Where did that originate?

Jean M
03-06-2013, 02:01 PM
@ DMXX - Delighted to assist. I should have posted earlier on this. Your mutation evidently travelled with the Indo-Europeans, being found among their descendants in both Europe and Asia.

DMXX
03-06-2013, 03:31 PM
Will start a new thread on 22018A shortly with some studies to get a better understanding of this mutation.

Just to add to the topic, an interesting study on Tibetans (who consume milk products) found none of five mutations for lactase persistence were present among them, indicating they developed lactase persistence independently from Europeans, Pakistanis and other populations.

Lactase persistence may have an independent origin in Tibetan populations from Tibet, China.
Peng MS, He JD, Zhu CL, Wu SF, Jin JQ, Zhang YP. Hum Genet. 2012 Jun;57(6):394-7. doi: 10.1038/jhg.2012.41. Epub 2012 May 10.



Milk consumption is prevalent in daily diets of Tibetans. To digest the milk sugar lactose, lactase persistence (LP) should be required. However, little is known about the genetic basis of LP in Tibetans. We screened 495 Tibetan individuals for five previously reported single-nucleotide polymorphisms (SNPs): -13907C/G (rs41525747), -13910C/T (rs4988235), -13915T/G (rs41380347), -14010G/C and -22018G/A (rs182549), which are associated with the LP in populations from a vast region surrounding Tibet. The five SNPs were nearly absent in Tibetan populations, suggesting LP likely to have an independent origin in Tibetans rather than to be introduced via gene flow from neighboring populations. We identified three novel SNPs (-13838G/A, -13906T/A and -13908C/T) in Tibetans. In particular, -13838G/A might be functional as it is located in the binding motif for HNF4α that acts as a transcription factor for intestinal gene expression. To investigate the potential association of this variant with LP, further detailed studies are required in the future.

Palisto
03-07-2013, 09:42 AM
There have been at least six separate mutations which cause the lactase switch-off to fail.


22018A or rs182549(C): first recognized in Finns. Generally found with 13910T in Europeans, but can appear as an independent cause of lactase persistence in Pakistanis and in the Kazakhs of Northern China.
13907G or rs41525747(C): East Africa
13910T or rs4988235(A): The dominant mutation in Western Eurasia and South Asia. In South Asia it decreases southward and eastward from a peak in the North-west. Also appears in Central Asia at lower levels: 30% for Kazakhs and 19% for Tajiko-Uzbeks.
13913C: Cameroon, Sudan, Ethiopia, and the Bedouin population in Saudi Arabia.
13915G or rs41380347(C) and 3712C (compound allele): Saudis and East Africans
14010C: East Africa


The paper above refers to GC-14010, which = 14010C.

I added two more SNP IDs to the list. I also wrote a post about it a while ago.
http://kurdishdna.blogspot.com/2012/06/lactose-tolerance.html


Ah! I finally have genotype proof of my lactose tolerance! I'm CC on rs182549. I do not have 13910T, so my lactose tolerance is of the same "Asiatic" type as Pakistanis and Kazakhs.

I checked rs182549 for 16 unrelated Kurds: 29 out of 32 alleles C (=91%) and 3 out of 32 alleles T (9%).
This is based on:
http://kurdishdna.blogspot.com/2012/08/allele-frequency-database-for-kurds.html

Other populations:
http://alfred.med.yale.edu/alfred/mvograph.asp?siteuid=SI001785V

DMXX
03-07-2013, 09:49 AM
Me, too! Previously, I was surprised to see how many Kurds are lactose intolerant at 23andme but physically lactose tolerant. I checked rs182549 for 16 unrelated Kurds: 29 out of 32 alleles C (=91%) and 3 out of 32 alleles T (9%).
This is based on:
http://kurdishdna.blogspot.com/2012/08/allele-frequency-database-for-kurds.html

Other populations:
http://alfred.med.yale.edu/alfred/mvograph.asp?siteuid=SI001785V

Prevalent lactose intolerance does not make sense for Iranians, Kurds or other Iranic-speaking groups because we all have a very dairy-rich diet. A staple breakfast in Iran includes plenty of goat's cheese with bread, cucumbers, tomatoes and a good cup of black tea. If it isn't 13910T, another mutation must be implicated.

[Edit]: As explained by Jean below, it looks like we (DMXX and the people of Kurdistan and Iran) are still on the lookout for our cause of lactase persistence. :D

Jean M
03-07-2013, 10:09 AM
So sorry to have misled people. I have checked http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs182549 after a nudge from DMXX and the ancestral form is C. So the lactase persistence type is rs182549(T).

Papers which refer to it are Enattah 2002; Ingram 2009; Bersaglieri 2004; Xu 2010.

Palisto
03-07-2013, 03:33 PM
So sorry to have misled people. I have checked http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs182549 after a nudge from DMXX and the ancestral form is C. So the lactase persistence type is rs182549(T).

Papers which refer to it are Enattah 2002; Ingram 2009; Bersaglieri 2004; Xu 2010.

The confusion is caused because the MCM6 gene is in the minus orientation and 23andme does not address it, all nucleotides are switched.