5 research outputs found
Unified Universal Seesaw Models
A set of Grand Unified Theories based upon the gauge groups SU(5)_\L \times
SU(5)_\R, SO(10)_\L \times SO(10)_\R and SU(4)_\C \times SU(4)_\L \times
SU(4)_\R is explored. Several novel features distinguish these theories from
the well-known , and SU(4)_\C \times SU(2)_\L \times SU(2)_\R
models which they generalize. Firstly, Standard Model quarks and leptons are
accompanied by and mix with heavy SU(2)_\L \times SU(2)_\R singlet partners.
The resulting fermion mass matrices are seesaw in form. Discrete parity
symmetries render the determinants of these mass matrices real and eliminate CP
violating gauge terms. The unified seesaw models consequently provide a
possible resolution to the strong CP problem. Secondly, \sinsq at the
unification scale is numerically smaller than the experimentally measured
scale value. The weak angle must therefore increase as it evolves down in
energy. Finally, proton decay is suppressed by small seesaw mixing factors in
all these theories.Comment: 22 pages with 2 figures not included but available upon request,
CALT-68-185
Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models
<p>Abstract</p> <p>Background</p> <p>Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias.</p> <p>Methods</p> <p>A cohort of 12 independently ascertained HNPCC families harbouring a founder MSH2 mutation was identified from a cancer genetics clinic in St. John's, Newfoundland, Canada. Carrier status was known for 247 family members but phenotype information on up to 85 additional relatives with unknown carrier status was available; using modified segregation models these additional individuals could be included in the analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of: any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer (EC) for females.</p> <p>Results</p> <p>Lifetime (age 70) risk estimates for male and female carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced substantially reduced lifetime risk for developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low lifetime risk for these two outcomes while male non-carriers had lifetime risks intermediate to the female carriers and non-carriers. Female carriers had a lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to non-carriers) were substantially greater for females compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were substantially greater for females compared to their male counterparts (Females = 23.7, 95%CI = (5.6, 137.9); Males = 6.8%, 95% CI = (2.3, 66.2)). However, the risk of developing CRC decreased with age among both genders.</p> <p>Conclusion</p> <p>The proposed modified segregation-based models used to estimate age-specific risks for HNPCC phenotypes can reduce bias due to ascertainment and missing genotype information as well as provide estimates of absolute and relative risks.</p