Indiana University-Purdue University Indianapolis (IUPUI) / This study investigated familial cases of cleft lip with or
without cleft palate to determine whether the unaffected members of each
family can be identified as gene carriers for the cleft trait. This
research presumes that such carriers will have henotypic features
identifiable by cephalometric analysis that are associated with an
increased risk to cleft offspring. Using population genetics
methodology, a pedigree analysis was made for each family member was
assigned to one of four groups: (1) obligate normal, (2) affected, (3)
carrier, and (4) unknown. LA and PA cephalographs were taken on each
subject and a clinical oral-facial examination carried out on
participating family members. Various anatomic landmarks located on the
LA and PA films were digitized and from them, a total of 28 linear
measurements were made. To eliminate the effect of sex and differential
age responses, Z scores were calculated.
Through univariate analysis, only one variable, NCR-MO, was shown
to be significantly different between the two groups. This variable
difference by itself is not adequate to differentiate those in the
normal group from the carrier group. Even though only one variable was
significant, other differences in the variables between these groups
become obvious when the group variables were plotted as Z scores. Since
Z scores are pure values with no limits (2--the number of standard
deviations in a given variable differs from normal). Thereby, age-related
growth differences were minimized. Further information is
gained when these Z scores are plotted as pattern profiles, Figures 5-7.
These profiles of mean Z scores for each variable pointed out
areas of the face in which the differences were so great that specific
anatomic areas appeared to be associated with one of the four groups.
For example, gene carriers demonstrated specific alterations in facial
height that might conceivably be used to discriminate that group from
the other three groups.
The family normals and carriers were then analyzed by using a
stepwise multivariate analysis. By this approach, a discriminant
function was generated consisting of six variables (three each from the
lateral and frontal headplates), which proved to be significant in
distinguishing an individual's phenotype. These variables define facial
height, width and depth. The specific findings included a decrease in
mid-facial height and depth along with an increased lower facial height
and width in the gene carrier population as compared to the normals.
The function then was used to predict group membership of the same
two groups. Comparing this analytical prediction to that of the
grouping system that resulted from the pedigree analysis, all but one
individual was classified correctly in both the normal and carrier
population.
A discriminant score was also determined for the unknown
population of family members which were defined as non-cleft blood
relatives of cleft probands. Thus, they were a mixture of two types--those
unaffected who carried a genetic liability for producing a cleft
child and those unaffected who did not. A prediction of their placement
into either the normal or carrier group was made with the discriminate
function. One-third were classed in the normal group and two-thirds as
gene carriers.
The results of this study confirm that the phenotype of these
unaffected family members designated as obligate gene carriers differs
significantly from that of the family normals. This information is not
only quite useful for genetic counselling but gives both a better
understanding or the genetic control of clefting and can lead to
molecular research to identify the specific gene in question.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/4182 |
| Date | January 1993 |
| Creators | Litz, Stephanie M. |
| Contributors | Bixler, David, Fleener, Donald E., Hennon, David Kent, 1933-, Sadove, A. Michael, Ward, Richard E., Avery, David R. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.158 seconds