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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.