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
RDA= 1000
micrograms/day
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/
Calcium Deficiency
RDA= 1000
micrograms/day
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/
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
T/T: 3x transcription of LCT
http://ghr.nlm.nih.gov/gene/MCM6
Homology
Species
Protein Name
% Similarity
# aa
Homo sapiens
MCM6
Mus musculus
Mcm6
96%
821 aa
Danio rerio
mcm6
82%
830 aa
Drosophila melanogaster
Mcm6
63%
817 aa
Caenorhabditis elegans
mcm-6
55%
810 aa
Saccharomyces cerevisiae
Mcm6
48%
1017 aa
Arabidopsis thaliana
MCM6
45%
831 aa
Domains:
Nucleic Acid Binding
821 aa
P-loop, AAA+
Homology
Species
Protein Name
% Similarity
# aa
Homo sapiens
MCM6
Mus musculus
Mcm6
96%
821 aa
Danio rerio
mcm6
82%
830 aa
Drosophila melanogaster
Mcm6
63%
817 aa
Caenorhabditis elegans
mcm-6
55%
810 aa
Saccharomyces cerevisiae
Mcm6
48%
1017 aa
Arabidopsis thaliana
MCM6
45%
831 aa
Domains:
Nucleic Acid Binding
821 aa
P-loop, AAA+
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’ AP2 Consensus
5' – CCC CCT GGC – 3’
5' – CTC CCT GGC– 3’
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’ AP2 Consensus
5' – CCC CCT GGC – 3’
5' – CTC CCT GGC– 3’
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 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
Perform a DNA Pull Down Assay
+ MudPIT
?
FUTURE STUDIES
Gastrointestinal Microbiome
http://www.springdaleclinic.com/the-5-ways-to-get-rid-of-nausea-related-toanxiety/
www.wzw.tum.de/bflm/index.php?id=11&L=1
http://commonfund.nih.gov/hmp/index.aspx
Gastrointestinal Microbiome
Compare the gastrointestinal microbiota
in humans, based on diet
in mice – intestinal biopsy
5' – CCC CCT GGC – 3’
5' – CTC CCT GGC– 3’
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): 46372. 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.