Biomedical subjects
K R Dronamraju
Publications and source records attributed to K R Dronamraju.
Gene therapy: false expectations?
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Regulation of human gene therapy.
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J.B.S. Haldane's (1892-1964) biological speculations.
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J.B.S. Haldane (1892-1964): centennial appreciation of a polymath.
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Sewall Wright (1889-1988).
The genetic contributions of Sewall Wright is briefly reviewed with special reference to J.B.S. Haldane's work. These include his work in population genetics, statistics, and animal breeding.
The origins of human gene mapping. With particular reference to the contributions of J. B. S. Haldane.
Methods in human gene mapping, including those developed by Bell and Haldane, Morton, and the more recent ones using somatic cell fusion, restriction fragment length polymorphism (RFLP), and multipoint linkage, are briefly reviewed.
Fetal mortality in oral cleft families (X): a response.
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Birth intervals in oral cleft families.
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Mammalian teratology and prenatal death.
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Fetal mortality in oral cleft families (IX): factors relating to the occurrence of sporadic clefts.
Pedigree data on 854 probands with cleft lip and/or cleft palate from the State of Indiana are presented. These include 123 probands with cleft lip alone (CL), 453 with cleft lip and palate (CLP), and 278 with isolated cleft palate (CP). Probands and families were interviewed at the Indiana University Medical Center during the years 1962-1980. Among features of special interest are an excess of bilateral CLP (46% of all CLP cases) and a significantly greater number of older mothers and fathers (over 34 years old) than in the general population. An apparent increase in the proportion of sporadic cases with time may be due to bias in ascertainment. It is suggested that the increased proportions of more severe clefts and older parents are among several factors which contribute to the incidence of fetal mortality in a cleft population. The association of fetal mortality with liability to clefting introduces a more precise way to define a sporadic cleft. That is, a truly sporadic cleft is one conceived as a single occurrence event and has survived to become a liveborn cleft child whereas other apparently sporadic cleft individuals represent the surviving cleft in a sibship in which fetal mortality has eliminated all other cleft offspring already conceived. This observation has applications to the collection and interpretation of genetic pedigree data for clefts as well as many other genetic conditions.
Fetal mortality in oral cleft families (V): Studies of sporadic vs familial and pure vs syndromic clefts.
The frequencies of fetal deaths in sibships of oral cleft probands are analysed in relation to sporadic or familial clefts, and pure or syndromic clefts. In a study of 1823 pregnancies in 630 sibships of probands with CL(P), the frequency of fetal deaths was found to be increased, but not significantly, in the sporadic group as compared to the familial group of sibships from Indiana. However, such an increase was found to be significant in the Montreal data. The pooled data from both these centers also show a significant increase in the sporadic group. For CP, no such differences were found. Similar comparisons of fetal mortality in relation to pure and syndromic clefts indicated that the frequencies of fetal deaths were consistently elevated in sibships of probands with syndromic clefts with one exception, which is the Indiana CP group where the lowest frequency of fetal deaths was observed in the sibships. This group mostly consisted of sibships with solitary pregnancies. This may have been a result of early zygotic mortality in this group. Further data will be obtained to confirm this observation.
Fetal mortality in oral cleft families (VII): Birth intervals.
Birth intervals in sibships of oral cleft probands are analysed to detect prolonged delays between successive pregnancies. Such intervals are useful indicators of undetected fetal mortality. The present study indicates that the average interval for 462 cleft families in Indiana is 30.61 months. The average interval leading to the birth of a cleft child is 33.94 and is significantly greater than the average interval for the entire sample. Although the contraception status of the Indiana population is not known, the significantly greater delay preceding the birth of a cleft child is indicative of a cause other than contraception. This finding is in agreement with the report by Drillien et al. (1966) that abnormal conceptions occur more frequently adjacent to cleft offspring. It is interesting that some increase in the average interval is also noted in the present study immediately following the birth of a cleft child. Such delays occurring both preceding and following the birth of a cleft child (in contrast to smaller intervals for other pregnancies in the same sibships) may indicate excessive fetal wastage due to a combination of genetic and environmental factors.
Fetal mortality in oral cleft families(IV): the "doubling effect".
Fetal mortality data from Lancaster, Penn., Chicago, Ill. and Minneapolis, Minn. are presented which support the authors' earlier findings in Indiana and Montreal that a positive relationship exists between the degree of liability to malformation and the incidence of fetal deaths in probands' sibships. Altogether, the study involved 189 CL sibships, 690 CLP sibships, and 3,416 pregnancies. On the basis of these data, which are derived from families of several different backgrounds of European ancestry, it is generalized that, as we proceed from CL sibships to CLP sibships, there is a doubling effect on fetal mortality. The consistency of this finding in several population samples is impressive. The implications of this observation are discussed with reference to genetic counseling.
Fetal mortality and cleft lip with or without cleft palate.
Analysis of fetal mortality in sibships of 406 probands with cleft lip with or without cleft palate (CL(P)) indicates that the incidence of fetal mortality is significantly greater in sibships of probands with bilateral CL(P) than in those of unilateral CL(P). The difference is even greater when fetal mortality in sibships of male probands with unilateral CL(P) is compared with that of female probands with bilateral CL(P). These findings support a multifactorial two-threshold concept in which a lower level of liability results in clefting while a higher level of liability causes fetal mortality.
Fetal mortality in oral cleft families: data from Indiana and Montreal.
Analysis of 418 sibships of oral cleft probands from Indiana, and 288 sibships from Montreal indicate that the incidence of fetal mortality is significantly greater in sibships of probands with cleft lip and cleft palate (CLP) as compared to that in sibships of probands with cleft lip (CL) alone. These findings support a multifactorial-two-threshold concept, according to which a lower level of liability results in clefting whereas a higher level of liability causes fetal deaths. They add confirmatory evidence in support of the authors' earlier work, utilizing data from two different sources.
Fetal mortality in oral cleft families (VI): a search for early embryonic and zygotic mortality.
A hypothesis concerning the detection of early embryonic and zygotic mortality in oral cleft families is presented. It is suggested that probands from solitary pregnancies are the result of a higher liability to clefting which eliminated potential siblings prior to the conception of the proband. A positive association between the degree of liability to clefting and fetal mortality has already been established by the authors' previous work. In sibships of solitary probands, such liability is assumed to have caused early embryonic and zygotic mortality which eliminated potential siblings and recognizable fetal loss. This hypothesis can be tested by an examination of the sex-ratios in probands from solitary pregnancies and those from multiple pregnancies. For CL(P), a decrease in the proportion of males would be expected in probands from solitary pregnancies in comparison to those from multiple pregnancies. For CP, however, an increase in the proportion of males in solitary probands is expected in comparison to those from multiple pregnancies. This hypothesis is applied to 613 CL(P) probands and 317 CP probands from Indiana. Although the expected decrease (for CL(P)) and increase (for CP) in the proportion of males in solitary probands is not quite significant, the trends are in the expected directions. It is suggested that the hypothesis should be tested further with additional data on oral clefts and other similar anomalies.
Fetal mortality associated with cleft lip and cleft palate.
Analysis of 1,516 pregnancies in sibships of probands with cleft lip with or without cleft palate [CL(P)], and 774 pregnancies in those of probands with isolated cleft palate (CP) indicated that fetal mortality significantly increases with liability to clefting. These data are compatible with the multifactorial two-threshold model, according to which a lower threshold level of liability results in a cleft formation whereas a higher level of liability causes a fetal death.