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MCM6 and Lactose Intolerance
Renae Geier
INTRODUCTION TO LACTOSE INTOLERANCE
Lactose Intolerance
http://www.springdaleclinic.com/the-5-ways-to-get-rid-of-nausea-related-to-anxiety/ http://www.mrbigben.com/food/dairy.html
Lactase Breaks Down Lactose
Troleson, 2005
Calcium Deficiency
http://astronutrition.com/lactase-enzyme-9000-fccl-units.html http://myculturedpalate.com/blog/2012/10/15/gaps-and-osteoporosis http://www.shopping.com/Viactiv-Viactiv-Calcium-Supplement-Soft-Chews-Milk-Chocolate-100-Count-Viactiv/info http://drliesa.com/eat-your-veggies-cruciferous-that-is/
RDA= 1000 micrograms/day
Calcium Deficiency
http://astronutrition.com/lactase-enzyme-9000-fccl-units.html http://myculturedpalate.com/blog/2012/10/15/gaps-and-osteoporosis http://www.shopping.com/Viactiv-Viactiv-Calcium-Supplement-Soft-Chews-Milk-Chocolate-100-Count-Viactiv/info http://drliesa.com/eat-your-veggies-cruciferous-that-is/
RDA= 1000 micrograms/day
http://idreamofbiochemistry.files.wordpress.com/2013/04/worldwide_prevalence_of_lactose_intolerance_in_recent_populations.jpg
INTRODUCTION TO MCM6
MCM6 Has A SNP That Enhances LCT 2q21
Gene Ontology:
DNA Replication
Nucleus
ATP and DNA binding
Bochman and Schwacha, 2009 http://ghr.nlm.nih.gov/gene/MCM6
MCM6 Has A SNP That Enhances LCT 2q21
http://ghr.nlm.nih.gov/gene/MCM6
T/T: 3x transcription of LCT
Homology
Arabidopsis thaliana MCM6 45%
821 aa
821 aa
830 aa
817 aa
810 aa
1017 aa
831 aa
Homo sapiens MCM6
Danio rerio mcm6 82%
P-loop, AAA+
Drosophila melanogaster Mcm6 63%
Mus musculus Mcm6 96%
Species Protein Name % Similarity # aa
Domains:
Caenorhabditis elegans mcm-6 55%
Saccharomyces cerevisiae Mcm6 48%
Nucleic Acid Binding
Homology
Arabidopsis thaliana MCM6 45%
821 aa
821 aa
830 aa
817 aa
810 aa
1017 aa
831 aa
Homo sapiens MCM6
Danio rerio mcm6 82%
P-loop, AAA+
Drosophila melanogaster Mcm6 63%
Mus musculus Mcm6 96%
Species Protein Name % Similarity # aa
Domains:
Caenorhabditis elegans mcm-6 55%
Saccharomyces cerevisiae Mcm6 48%
Nucleic Acid Binding
EXPERIMENTS
People with LI have a SNP at -13910
Hypothesis 1: The -13910 nucleotide affects the binding of a transcription factor, AP2, which affects lactase expression
5' – GCC NNNGGC – 3’
5' – CCC CCT GGC – 3’
5' – CTC CCT GGC– 3’
AP2 Consensus
People with LI have a SNP at -13910
Hypothesis 1: The -13910 nucleotide affects the binding of a transcription factor, AP2, which affects lactase expression
5' – GCC NNNGGC – 3’
5' – CCC CCT GGC – 3’
5' – CTC CCT GGC– 3’
AP2 Consensus
Hypothesis 1: The -13910 nucleotide affects the binding of a transcription factor, AP2, which affects lactase expression
AP2
People with LI have a SNP at -13910
Hypothesis 1: The -13910 nucleotide affects the binding of a transcription factor, AP2, which affects lactase expression
AP2
People with LI have a SNP at -13910
Hypothesis 2: The -13910 nucleotide affects the binding of an unknown transcription factor which affects lactase expression
?
People with LI have a SNP at -13910
Perform a DNA Pull Down Assay + MudPIT
FUTURE STUDIES
http://commonfund.nih.gov/hmp/index.aspx
Gastrointestinal Microbiome
http://www.springdaleclinic.com/the-5-ways-to-get-rid-of-nausea-related-to-anxiety/ www.wzw.tum.de/bflm/index.php?id=11&L=1
Gastrointestinal Microbiome
5' – CCC CCT GGC – 3’ 5' – CTC CCT GGC– 3’
Compare the gastrointestinal microbiota in humans, based on diet in mice – intestinal biopsy
http://www.columbia.edu/cu/biology/courses/w2501/Histopictures/Smallintestine_highpower.jpg
References Bochman, M. L., and A. Schwacha. "The Mcm Complex: Unwinding the Mechanism of a Replicative Helicase."
Microbiology and Molecular Biology Reviews 73.4 (2009): 652-83. American Society for Microbiology. Web. 8 May 2013.
Delgado, Susana, Raul Cabera-Rubio, Alex Mira, Adolfo Suarez, and Baltasar Mayo. "Microbiological Survey of the Human Gastric Ecosystem Using Culturing and Pyrosequencing Methods." Microbial Ecology 65 (2013): 763-72. Springer. Web. 28 Apr. 2013.
Grenham, Sue, Gerard Clarke, John F. Cryan, and Timothy G. Dinan. "Brain–gut–microbe Communication in Health and Disease." Frontiers in Physiology 2.94 (2011): n. pag.Frontiers in Gastrointestinal Science. Web. 1 May 2013.
He, Tao, Marion G. Priebe, Hermie JM Harmsen, Frans Stellaard, Xiaohong Sun, Gjalt W. Welling, and Roel J. Vonk. "Colonic Fermentation May Play a Role in Lactose Intolerance in Humans." The Journal of Nutrition 136.1 (2006): 58-63. The American Society for Nutrition. Web. 1 May 2013.
Prasad, Jaya, Sunil Sazawal, Usha Dhingra, and Pramod K. Gopal. "Detection of Viable Bifidobacterium Lactis HN019 in Stools of Children during a Synbiotic Dietary Intervention Trial." International Dairy Journal 30 (2013): 64-67. SciVerse Science Direct. Web. 27 Apr. 2013.
Takaishi, H., T. Matsuki, A. Nakazawa, T. Takada, S. Kado, T. Asahara, N. Kamada, A. Sakuraba, T. Yajima, and H. Higuchi. "Imbalance in Intestinal Microflora Constitution Could Be Involved in the Pathogenesis of Inflammatory Bowel Disease."International Journal of Medical Microbiology 298.5-6 (2008): 463-72. Science Direct. Web. 1 May 2013.
Troelsen, Jesper T. "Adult-type Hypolactasia and Regulation of Lactase Expression." Biochimica Et Biophysica Acta (BBA) - General Subjects 1723.1-3 (2005): 19-32. Web. 6 Feb. 2013.
Sahi, T. "Genetics and Epidemiology of Adult-type Hypolactasia." Scandinavian Journal of Gastroenterology 29 (1994): 7-20. Web. 31 Jan. 2013.