And Daddy Makes 3.

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And Daddy Makes 3.
Sam Christensen DDS 05
Phil Fletcher DDS 05
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Project Title
The role of paternal methylenetetrahydrofolate
reductase (MTHFR) in the etiology of cleft lip
and palate anomalies
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Background
Maternal Folate Intake
Step 1. High Adequate Deficient
Maternal Genotype
Maternal Folate Transport and Metabolism
Step 2. High Adequate Deficient
Fetal Genotype
Fetal Folate Transport and Metabolism
Step 3. High Adequate Deficient
Nonaffected Infant
M. Tolarova M.D. Ph.D. D.Sc.
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Background
Maternal Folate Intake
Step 1. High Adequate Deficient
Maternal Genotype
Maternal Folate Transport and Metabolism
Step 2. High Adequate Deficient
Fetal Genotype
Fetal Folate Transport and Metabolism
Step 3. High Adequate Deficient
Affected Infant
M. Tolarova M.D. Ph.D. D.Sc.
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Background
Maternal Folate Intake
Step 1. High Adequate Deficient
Maternal Genotype
Maternal Folate Transport and Metabolism
Step 2. High Adequate Deficient
Fetal Genotype
Fetal Folate Transport and Metabolism
Step 3. High Adequate Deficient
Affected Infant
M. Tolarova M.D. Ph.D. D.Sc.
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Background
Maternal Folate Intake
Step 1. High Adequate Deficient
Maternal Genotype
Maternal Folate Transport and Metabolism
Step 2. High Adequate Deficient
Fetal Genotype
Fetal Folate Transport and Metabolism
Step 3. High Adequate Deficient
Affected Infant
M. Tolarova M.D. Ph.D. D.Sc.
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Background
MTHFR has been suggested as a candidate gene for
CL/P anomalies. However, etiological studies of
CL/P have, in large part, centered on both
maternal and fetal genotypes, especially with
respect to MTHFR, and have largely ignored the
genetic contribution of the father.
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Hypothesis
The 677ct mutation of MTHFR in fathers is
contributing significantly to the prevalence of
clefting in Guatemala.
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Significance
From the perspective of the mother and the fetus,
fetal development is dependent on both genetic
and environmental factors. That said, the
fathers contribution to fetal development is
purely genetic. If we can determine how much the
paternal genotype contributes to cleft lip and
palate anomalies, preventative measures can be
taken for those individuals who are most at risk.
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Plan
1) Obtain blood spot DNA samples from a cross
section of males in Guatemala
2) Determine the prevalence of the 677ct MTHFR
mutation in Guatemalan males through DNA
extraction and PCR
3) Examine the genotypes of Guatemalan fathers
who have children with CL/P
4) Make a statistical comparison and analysis of
CL/P fathers genotypes with that of the mothers
and their children
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References
Lian ZH, Zack MM, Erickson JD (1986) Paternal age
and the occurrence of birth defects. Am J Hum
Genet. 1986 Nov39(5)648-60 PubMed Martinelli
M, Scapoli L, Pezzetti F, Carinci F, Carinci P,
Stabellini G, BiscegliaL, Gombos F, Tognon M
(1998) C677T variant form at the MTHFR gene and
CL/P a risk factor for mothers? Am J Med Genet.
2001 Feb 1 98(4) 357-60 PubMed Molloy AM,
Mills JL, Kirke PM, Ramsbottom D, McPartlin JM,
Burke H, Conley M, Whitehead AS, Weir DG, Scott
JM. Low blood folates in NTD pregnancies are only
partly explained by thermolabile
5,10-methylenetetrahydrofolate reductase low
folate status alone may be the critical factor.
Am J Med Genet. 1998 Jun 3078(2)155-9
PubMed Olshan AF, Teschke K, Baird PA (1991)
Paternal occupation and congenital anomalies in
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PubMed Samadder P, Evans JA, Chudley AE.
Segregation analysis of rare autosomal folate
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PubMed Shields DC, Kirke PM, Mills JL,
Ramsbottom d, Molloy AM, Burke H, Weir DG, Scott
JM, Whitehead AS (1998) The Thermolabile
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and Neural Tube Defects An Evaluation of Genetic
Risk and the Relative Importance of the Genotypes
of the Embryo and the Mother. Am J Hum Genet.
1999 Apr64(4) 1045-55 PubMed Zhang J, Savitz
DA, Schwingl PJ, Cai WW (1992) A case-control
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