[Determination and inheritance of the sex in various Oniscoidea. II. Inheritance of monogeny in Cylisticus convexus].
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Animals↗
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Studies on the inherited susceptibility and inherited hormonal influence in the genesis of mammary cancer in mice.
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Animals↗
Barrett's esophagus: inherited epithelium or inherited reflux?
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Adolescent↗
Animal models of inherited metabolic diseases. Proceedings of the International Symposium on Animal Models of Inherited Metabolic Disease. Bethesda, Maryland. October 19-20, 1981.
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Animals↗
The inheritance of organelle genes and genomes: patterns and mechanisms.
Unlike nuclear genes and genomes, the inheritance of organelle genes and genomes does not follow Mendel's laws. In this mini-review, I summarize recent research progress on the patterns and mechanisms of the inheritance of organelle genes and genomes. While most sexual eukaryotes show uniparental inheritance of organelle genes and genomes in some progeny at least part of the time, increasing evidence indicates that strictly uniparental inheritance is rare and that organelle inheritance patterns are very diverse and complex. In contrast with the predominance of uniparental inheritance in multicellular organisms, organelle genes in eukaryotic microorganisms, such as protists, algae, and fungi, typically show a greater diversity of inheritance patterns, with sex-determining loci playing significant roles. The diverse patterns of inheritance are matched by the rich variety of potential mechanisms. Indeed, many factors, both deterministic and stochastic, can influence observed patterns of organelle inheritance. Interestingly, in multicellular organisms, progeny from interspecific crosses seem to exhibit more frequent paternal leakage and biparental organelle genome inheritance than those from intraspecific crosses. The recent observation of a sex-determining gene in the basidiomycete yeast Cryptococcus neoformans, which controls mitochondrial DNA inheritance, has opened up potentially exciting research opportunities for identifying specific molecular genetic pathways that control organelle inheritance, as well as for testing evolutionary hypotheses regarding the prevalence of uniparental inheritance of organelle genes and genomes.
Animals↗
Inferring mode of inheritance by comparison of lod scores.
One usually must assume a mode of inheritance when using lod scores for linkage analysis. In this study, we asked the question, "If one assumed mode of inheritance in a linkage analysis gives a higher lod score than another, does that indicate that the mode of inheritance that led to the higher lod score is more 'correct' than the other?" We simulated data under a variety of penetrances, assuming either dominant or recessive inheritance. We then analyzed those simulated data under the correct mode of inheritance, assuming a range of penetrance values, and under the incorrect model, also assuming a range of penetrance values. We found that, if there was enough information for a maximum lod score of at least 3.0, assuming the correct penetrance value or mode of inheritance in the analysis led to a higher lod score than assuming the incorrect penetrance or the incorrect mode of inheritance. These results cannot yet be generalized outside of the specific modes of inheritance and penetrance combinations that we have modeled. Also, penetrance was modeled as "random." The effect of "reduced penetrance" caused by other genetic factors has not yet been tested. We also tested the effect of non-standard ascertainment on drawing conclusions about mode of inheritance from linkage data. Even when families were ascertained only if the family was multiplex (i.e., more than one affected sib), assuming the correct mode of inheritance gave a higher lod score than assuming the incorrect mode of inheritance. This method has the promise of both simplifying and expanding the application of linkage analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Inheritance pattern of Beckwith-Wiedemann syndrome is heterogeneous in 291 families with an affected proband.
Beckwith-Wiedemann syndrome (BWS) is congenital disorder whose molecular etiology is related to genetic and epigenetic mutations on 11p15. The majority of cases of BWS are sporadic, but a substantial proportion are familial, with an unknown inheritance pattern, although autosomal dominant and sex-dependent inheritance have been proposed. We tested the hypothesis that in familial BWS, autosomal dominant inheritance is the primary mode of transmission underlying familial instances. Segregation analysis was performed in 291 families ascertained with an affected child. Individuals were considered to have BWS if they had two of five major features: macroglossia, macrosomia, hypoglycemia at birth, abdominal wall defect, and ear pits or creases. Models of inheritance were tested using pedigree analysis package (PAP) parameterized for a discrete trait. A total of 291 families of an affected proband were included in the study. The analysis was based on a revised general model that included a boundary solution. Sporadic and environmental models were rejected. Overall, the results suggested Mendelian inheritance but under recessive or additive mode of inheritance, which fit the data equally well rather than dominant inheritance. However, the presence of families in the cohort consistent with dominant and sex-dependent inheritance suggest familial BWS may be a heterogeneous group comprised of different inheritance patterns. Familial BWS does not appear to be consistent with autosomal dominant transmission, and is likely a complex mixture of different inheritance patterns.
Beckwith-Wiedemann Syndrome↗
Rates of mutant and inherited structural cytogenetic abnormalities detected at amniocentesis: results on about 63,000 fetuses.
We report data on diagnoses made on amniotic fluid specimens from 1977 to 1984 as reported to the New York State Chromosome Registry. The rate of all de novo (presumed mutant) abnormalities was about 2 per 1,000 in about 61,000 fetuses in which results are unlikely to be biased by the reason for amniocentesis (except for maternal age). This includes about 0.5 per 1,000 de novo markers, about 0.5 per 1,000 other de novo unbalanced, and about 1.0 per 1,000 de novo balanced rearrangements. In about 55,000 fetuses in which rates of inherited abnormalities could be evaluated without apparent bias, the rate of all inherited rearrangement was about 2.9 per 1,000. This includes about 0.3 per 1,000 inherited markers, about 0.2 per 1,000 other inherited unbalanced rearrangements, and about 2.4 per 1,000 inherited balanced abnormalities. Only mutant markers showed a clear association with maternal age (37.6 +/- 2.7 in 24 cases v. 35.8 +/- 3.6 in controls). Inherited markers did not exhibit this trend (35.8 +/- 2.0 in 12 cases v. 36.4 +/- 2.8 in controls). Paternal age does not appear to account for the association. Among abnormalities of known origin, the ratio of mutant to inherited cases is for markers 64:36, for other unbalanced rearrangements 73:27, and for all balanced abnormalities 29:71. In a subgroup of about 55,000 fetuses, of 263 total abnormalities there were 8 instances of apparent true somatic mosaics (5 mutant and 3 of unknown origin but almost certainly mutant). There were also 20 instances of markers in which presumptive somatic loss had resulted in mosaicism (10 mutant, 6 of unknown origin and 4 inherited) and 13 other instances of mosaicism associated with apparent somatic loss (9 mutant, 3 of unknown origin, and 1 inherited). The sex ratio (Y to non-Y karyotypes) for all abnormalities detected was 228:210 (1.09), not different from controls. Only deletions (5:14) and 'other' unbalanced rearrangements (5:13) exhibited a suggestive deviation from this trend. The rates of mutant chromosome rearrangements reported from 1977 to 1983 showed no apparent time cluster, with the possible exception of a peak of markers in 1977, a trend that may be due to higher maternal age in this year. Among fetuses studied because of maternal exposure to putative mutagens there was a non-significant excess of mutants (2.9-5.7 per 1,000 v. 1.7-2.2 per 1,000) and a borderline significant excess of inherited rearrangements (8.6-11.5 per 1,000 v. 2.6-3.1 per 1,000).(ABSTRACT TRUNCATED AT 400 WORDS)
Amniocentesis↗
Inherited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, parental-age associations, sex-ratio trends, and comparisons with rates of mutants.
Rates of structural chromosome abnormalities were analyzed in 24,951 fetuses studied prenatally in which there were no grounds to suspect an inherited abnormality. In about one in 200 prenatal cytogenetic diagnoses, an unexpected structural abnormality was found. The observed rate was 5.3 per 1,000, of which 1.7 per 1,000 were unbalanced and 3.6 per 1,000 balanced. The rate of inherited abnormalities was 3.1-3.7 per 1,000 (0.4-0.9 per 1,000 for unbalanced abnormalities and 2.6-2.8 per 1,000 for balanced abnormalities). The rate of mutants in this series was, by contrast, 1.6-2.2 per 1,000 (0.8-1.2 per 1,000 for unbalanced abnormalities and 0.8-1.0 per 1,000 for balanced abnormalities). The rate of balanced Robertsonian translocation carriers was 0.6 per 1,000 (about 0.25 per 1,000 for mutants and 0.35 per 1,000 for inherited abnormalities), and for other balanced abnormalities, 3.0 per 1,000 (about 0.6 per 1,000 for mutants and 2.4 per 1,000 for inherited abnormalities). The rates of unbalanced Robertsonian translocations was about 0.1 per 1,000, almost all of which were mutants. For supernumerary rearrangements, the rate was 0.9 per 1,000 (about 0.4 per 1,000 inherited and 0.5 per 1,000 mutant). The rates of all unbalanced (nonmosaic) inherited abnormalities (4.0-5.2 per 10,000) were intermediate between higher rates estimated in all conceptuses (9.1-15.8 per 10,000) and rates observed in newborns (1.5-2.5 per 10,000). This trend is probably attributable to fetal mortality associated with unbalanced rearrangements. The rates of balanced (nonmosaic) inherited abnormalities (26.0-28.0 per 10,000), however, were considerably higher than the rates in all conceptuses (13-16.7 per 10,000) or in all live births (12.2-16.0 per 10,000). The major difference was in the rate of inversions. The use of "banding" methods in the studies of amniocentesis but not in most of the live births or abortus studies probably contributes to at least some of these differences. One trend in parental age among the inherited abnormalities was noteworthy. Paternal age was elevated for inherited balanced reciprocal structural abnormalities of paternal origin but not of maternal origin. With regard to sex ratio, there was a greater proportion of females than males among the unbalanced rearrangements both inherited and mutant. There was no obvious sex difference among the balanced rearrangements.
Adult↗
Using lod-score differences to determine mode of inheritance: a simple, robust method even in the presence of heterogeneity and reduced penetrance.
Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method (maximized maximum lod score or mod score) and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference (delta) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if delta was > 1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a delta of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of alpha, the fraction of linked families in the data set, although the reliability decreased slightly as alpha fell below .50.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
The mating type-specific homeodomain genes SXI1 alpha and SXI2a coordinately control uniparental mitochondrial inheritance in Cryptococcus neoformans.
In the great majority of sexual eukaryotes, mitochondrial genomes are inherited almost exclusively from a single parent. While many hypotheses have been proposed to explain this phenomenon, very little is known about the genetic elements controlling uniparental mitochondria inheritance. In the bipolar, isogamous basidiomycete yeast Cryptococcus neoformans, progeny from crosses between strains of mating type a (MATa) and mating type alpha (MATalpha) typically inherit mitochondrial DNA (mtDNA) from the MATa parent. We recently demonstrated that a mating type alpha (MATalpha)-specific gene SXI1a, controls mitochondrial inheritance in C. neoformans. Here, we show that another homeodomain gene SXI2a in the alternative mating type MATa is also required for uniparental mtDNA inheritance in this fungus. Disruption of SXI2a resulted in biparental mtDNA inheritance in the zygote population with significant numbers of progeny inheriting mtDNA from the MATa parent, the MATalpha parent, and both the MATa and the MATalpha parents. In addition, progeny from same-sex mating between MATalpha strains showed a biparental mitochondrial inheritance pattern. Our results suggest that SXI1alpha and SXI2a coordinately control uniparental mitochondrial inheritance in C. neoformans.
Cryptococcus neoformans↗
Pregnancy complications in women with inherited thrombophilia.
OBJECTIVE: The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications. METHODS: All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000-2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. RESULTS: Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9-10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5-16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3-10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4-15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90-10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age. CONCLUSION: Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.
Blood Coagulation Disorders, Inherited↗
Gynaecological and obstetric management of women with inherited bleeding disorders.
OBJECTIVE: The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. OPTIONS: Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. EVIDENCE: A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. RECOMMENDATIONS: 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).
Journal Article↗
Gynaecological and obstetric management of women with inherited bleeding disorders.
OBJECTIVE: The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. OPTIONS: Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. EVIDENCE: A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. RECOMMENDATIONS: 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).
Blood Coagulation Disorders↗
Identification of chromosome inheritance modifiers in Drosophila melanogaster.
Faithful chromosome inheritance is a fundamental biological activity and errors contribute to birth defects and cancer progression. We have performed a P-element screen in Drosophila melanogaster with the aim of identifying novel candidate genes involved in inheritance. We used a "sensitized" minichromosome substrate (J21A) to screen approximately 3,000 new P-element lines for dominant effects on chromosome inheritance and recovered 78 Sensitized chromosome inheritance modifiers (Scim). Of these, 69 decreased minichromosome inheritance while 9 increased minichromosome inheritance. Fourteen mutations are lethal or semilethal when homozygous and all exhibit dramatic mitotic defects. Inverse PCR combined with genomic analyses identified P insertions within or close to genes with previously described inheritance functions, including wings apart-like (wapl), centrosomin (cnn), and pavarotti (pav). Further, lethal insertions in replication factor complex 4 (rfc4) and GTPase-activating protein 1 (Gap1) exhibit specific mitotic chromosome defects, discovering previously unknown roles for these proteins in chromosome inheritance. The majority of the lines represent mutations in previously uncharacterized loci, many of which have human homologs, and we anticipate that this collection will provide a rich source of mutations in new genes required for chromosome inheritance in metazoans.
Animals↗
Inheritance of organelle DNA sequences in a citrus-poncirus intergeneric cross.
Many land plants deviate from the maternal pattern of organelle inheritance. In this study, heterologous mitochondrial and chloroplast probes were used to investigate the inheritance of organelle genomes in the progeny of an intergeneric cross. The seed parent was LB 1-18 (a hybrid of Citrus reticulata Blanco cv. Clementine x C. paradisi Macf. cv. Duncan) and the pollen parent was the cross-compatible species Poncirus trifoliata (L.) Raf. All 26 progeny examined exhibited maternal inheritance of plastid petA and petD loci. However, 17 of the 26 progeny exhibited an apparent biparental inheritance of mitochondrial atpA, cob, coxII, and coxIII restriction fragment length polymorphisms (RFLPs) and maternal inheritance of mitochondrial rrn26 and coxI RFLPs. The remaining nine progeny inherited only maternal mitochondrial DNA (mtDNA) configurations. Investigations of plant mitochondrial genome inheritance are complicated by the multipartite structure of this genome, nuclear gene control over mitochondrial genome organization, and transfer of mitochondrial sequences to the nucleus. In this study, paternal mtDNA configurations were not detected in purified mtDNA of progeny plants, but were present in progeny DNA preparations enriched for nuclear genome sequences. MtDNA sequences in the nuclear genome therefore produced an inheritance pattern that mimics biparental inheritance of mtDNA.
Citrus↗
Effect of heterogeneity and assumed mode of inheritance on lod scores.
Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic Linkage↗
Family study of the inheritance of pectus excavatum.
BACKGROUND: The most common congenital deformity of the chest wall is pectus excavatum, a malformation that is present in between 1 in 400 and 1 in 1000 live births and causes the body of the sternum to be displaced, producing a depression. There are many different shapes of the pectus, and multiple factors probably contribute to the final form. The etiology of pectus excavatum is uncertain, but a familial tendency has been found in clinical experience, where it may be seen in more than one sibling. Pectus excavatum is commonly associated with connective tissue disorders such as Marfan and Ehlers Danlos syndromes. Extensive literature review failed to identify articles documenting families with multiple affected members. PURPOSE: The purpose of this study was to collect evidence that pectus excavatum is familial and may be an inherited disorder. METHODS: Using the Children's Surgical Specialty Group database at Children's Hospital of The King's Daughters, families with more than one affected individual were selected. With Institutional Review Board-approved informed consent, 34 families agreed to participate. Family histories were obtained, and a 4-generation pedigree was constructed for each family. Forty questions were asked about each individual's medical history, and comprehensive systems review included features of connective tissue-related problems. Inheritance patterns for each family were determined by pedigree analysis. RESULTS: A total of 14 families suggested autosomal dominant inheritance, 4 families suggested autosomal recessive inheritance, and 6 families suggested X-linked recessive inheritance. Ten families had complex inheritance patterns. Pectus excavatum occurred more frequently in males than in females (1.8:1). Long arms, legs, and fingers; high-arched palate; mitral valve prolapse; heart arrhythmia; scoliosis; double jointedness; flexibility; flat feet; childhood myopia; poor healing; and easy bruising were commonly associated with pectus excavatum. CONCLUSIONS: Pedigree analysis of 34 families provides evidence that pectus excavatum is an inherited disorder, possibly of connective tissue. Although some families demonstrate apparent Mendelian inheritance, most appear to be multifactorial.
Female↗