Thesis (M.S.)--University of Michigan, 1978.

Thesis (M.S.)--University of Michigan, 1978.

Thesis (M.S.)--University of Michigan, 1961.

Thesis (M.S.)--University of Michigan, 1970.

Thesis (M.S.)--University of Wisconsin--Madison, 1965. / eContent provider-neutral record in process. Description based on print version record. Bibliography: l. 116-129.

Thesis (MA)--University of Chicago. / Includes bibliographical references.

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns born over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.

Indiana University-Purdue University Indianapolis (IUPUI)

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.

No description available.