Nonallelic noncomplementation models in mice: The first arch and lidgap-Gates mutations

Genome ◽  
1998 ◽  
Vol 41 (6) ◽  
pp. 789-796 ◽  
Author(s):  
M J Harris ◽  
D M Juriloff
Keyword(s):  
Birth Defects ◽  
Birth Defect ◽  
Reciprocal Cross ◽  
Threshold Model ◽  
Complementation Test ◽  
Double Heterozygote ◽  
Mapping Data ◽  
Developmental Threshold ◽  
Developmental Thresholds ◽  
Genetic Context

We tested for complementation between two Mendelian mutations in mice, Far (first arch) and lgGa (lidgap-Gates). Each of these mutations gives greater than 70% risk of the birth defect, open eyelids, in homozygotes and gives little or no risk in heterozygotes. Far and lgGa are known to not be alleles; Far maps to Chr 2 and lgGamaps to Chr 13. However, the cross between +/Far (on the BALB/cGaBc strain) and lgGa/lgGa (on the LGG/Bc strain) gave 32% (48/149) of progeny affected with open eyelids at birth: 63% (45/71) of the double heterozygote, +/Far, +/lgGa, compared with 4% (3/78) of the +/+, +/lgGa progeny. That is, the complementation test suggests that Far andlgGa are alleles, whereas the mapping data show that they are not. We interpret the result of the Far by lgGa test as an example of nonallelic noncomplementation (or "false allelism") in mammals, and suggest that this phenomenon might be expected because open eyelids at birth involves a developmental threshold. Our data also show that both the embryonic and the maternal background genotypes strongly influence the risk of open eyelids in the Far by lgGa crosses. The risk to the double heterozygote (+/Far, lgGa) is highest (77%) with Far from the BALB/cGaBc rather than the ICR/Bc (0%) strain and in a BALB/cGaBc (77%) rather than an LGG/Bc (50%) dam in the reciprocal cross. This effect of genetic context on risk is also predicted by the threshold model. Based on our data on open eyelids at birth, we suggest that false allelism may be common in mammalian birth defects that result from failure to meet developmental thresholds, even when the "causal" mutations are Mendelian.Key words: digenic, false allelism, open eyelids, Far, threshold.

scholarly journals Periconceptional folic acid intake in Northwest Russia: a birth registry study

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
V A Postoev ◽  
L I Menshikova ◽  
A A Usynina ◽  
A M Grjibovski ◽  
J O Odland
Keyword(s):  
Folic Acid ◽  
Birth Defects ◽  
Birth Defect ◽  
Demographic Factors ◽  
Folic Acid Supplementation ◽  
Demographic Characteristics ◽  
Prenatal Counseling ◽  
Folic Acid Intake ◽  
Birth Registry ◽  
Socio Demographic Factors

Abstract Introduction Periconceptional use of folic acid supplementation is an evidence-based measure of birth defects prevention. The study was aimed to assess effect of periconceptual use of folic acid on birth defect prevalence in Arkhangelsk county and to investigate socio-demographic factors, which are associated with adherence to this preventive measure. Methods A registry-based study was conducted with data from the Arkhangelsk County Birth Registry for 2012-2015. The study population included 57084 pregnancies to calculate the proportion of women taking folic acid and 53340 pregnancy outcomes without missing data to analyze related socio-demographic characteristics. Results The proportion of women followed a folic acid supplementation before pregnancy was 1.3% (95% CI: 1.2-1.4), during pregnancy - 55.8% (95%CI: 54.6-56.4). Such women had less risk to deliver a newborn with any birth defects (OR = 0,84, 95%CI: 0,75 - 0,95). Considering birth defects prevalence of 38,6 per 1000 newborns in Arkhangelsk county, number needed to prevent one case of birth defect was 142,9. Based on multivariate analysis, nulliparous married women with higher education, aged 30 or more, had a higher chance to use folic acid before and during pregnancy. The history of spontaneous abortion in the mother's medical history and the first pregnancy were negatively associated with the probability of folic acid intake both before and during pregnancy. Conclusions The compliance to periconceptional intake of folic acid among women in the region was low. A level of compliance was associated with such socio-demographic factors as age, education, marital status, gravidity and parity. The findings have direct applications in improving prenatal care in Arkhangelsk county and establishing targets for prenatal counseling. Key messages A level of compliance to primary prevention of birth defects is associated with such socio-demographic factors as age, education, marital status, gravidity and parity. Prenatal counseling in terms of birth defects prevention should be based on socio-demographic characteristics of pregnant women.

Pregnancy Experience after Delivery of a Child with a Major Birth Defect: A Population Study

PEDIATRICS ◽  
1995 ◽  
Vol 95 (1) ◽  
pp. 59-65
Author(s):  
Margarett K. Davis ◽  
Muin J. Khoury ◽  
J. David Erickson
Keyword(s):  
Birth Defects ◽  
Reproductive Behavior ◽  
Birth Defect ◽  
Large Population ◽  
Population Based ◽  
Subsequent Pregnancy ◽  
Pregnancy Rates ◽  
Wide Range ◽  
First Year Of Life ◽  
And Control

Objective. Data from a large population-based, case-control study were analyzed to determine whether women giving birth to children with major birth defects have different subsequent pregnancy patterns than those giving birth to live-born babies without defects. Other studies examining this phenomenon have been smaller, have not been population-based, or have not addressed the different effects that a wide range of major defects might have on mothers' subsequent pregnancy rates. Methods. Mothers of 4918 infants with major birth defects born from 1968 through 1980 in metropolitan Atlanta were compared with mothers of 3029 control infants, frequency-matched on birth year, birth hospital, and race. Results. The pregnancy rate in the first 3 years after the index birth was higher among case mothers (36%) than among control mothers (30%, P < .0001). This excess was seen for mothers of stillborn case infants (64%) and mothers of case infants who died in infancy (58%), but not for mothers of case infants who survived the first year of life (31%). Pregnancy rates varied by birth defect type. Maternal and infant factors varied among case and control subjects and influenced subsequent pregnancy rates. Conclusion. The reproductive behavior observed in this study supports the theory that mothers of nonsurviving children with birth defects compensate by acting to "replace" the lost child. Reproductive behavior was also strongly associated with having completed a previous pregnancy and by the type of birth defect.

scholarly journals Thermal requirements and estimated number of generations of Neopamera bilobata (Say) in strawberry-producing regions of Brazil

2017 ◽  
Vol 48 (1) ◽  
Author(s):  
Taciana Melissa de Azevedo Kuhn ◽  
Alci Enimar Loeck ◽  
Marcos Botton
Keyword(s):  
Adult Stage ◽  
Thermal Constant ◽  
Rio Grande Do Sul ◽  
Degree Days ◽  
Climate Chamber ◽  
Thermal Threshold ◽  
Developmental Threshold ◽  
Thermal Requirements ◽  
Developmental Thresholds ◽  
The Mean

ABSTRACT: The thermal threshold and thermal requirements of Neopamera bilobata were determined, and the number of generations that this species may produce in the main strawberry-producing regions of Brazil was estimated. In a climate chamber (70±10% RH and 12h photophase) at 16, 19, 22, 25, 28, or 30±1°C, the development of 120 eggs was monitored until the adult stage, at each temperature. Nymphs were maintained in individual cages and fed on strawberry fruits of the cultivar Aromas. The mean duration and viability of the egg and nymph stages were calculated by estimating the lower and upper developmental thresholds and the thermal constant, and this information was used to estimate the number of generations per year in different strawberry-producing regions of Brazil. The egg-to-adult duration decreased as temperatures increased, up to 28°C (93.4, 83.2, 43.9, and 31.4 days at 19, 22, 25, and 28°C, respectively). Viability of nymphs was highest between 22 and 28°C. At 30°C, the egg-to-adult duration increased (36 days), while the viability decreased (11.11%). The lower egg-to-adult developmental threshold was 15.2°C and the thermal constant was 418.4 degree-days. Calculating the number of generations indicated that the largest number (5.1 generations yr-1) was obtained for the municipality of Jaboti, Paraná, and the smallest for Caxias do Sul, Rio Grande do Sul (1.9 generations yr-1). Our findings demonstrated that important strawberry-producing regions in Brazil are suitable for the development of N. bilobata.

scholarly journals Burden and consequence of birth defects in Nepal-evidence from prospective cohort study

2021 ◽  
Author(s):  
Prajwal Paudel ◽  
Avinash K Sunny ◽  
Rejina Gurung ◽  
Abhishek Gurung ◽  
Honey Malla ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Birth Defects ◽  
Prospective Cohort ◽  
Birth Defect ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Birth Asphyxia ◽  
Neonatal Infection

Abstract Background-Every year an estimated 7.9 million babies are born with birth defect. Of these babies, more than 3 million die and 3.2 million have disability. Improving nationwide information on prevalence of birth defect, risk factor and consequence is required for better resource allocation for prevention, management and rehabilitation. In this study, we assess the prevalence of birth defect, associated risk factors and consequences in Nepal.Method-This is a prospective cohort study conducted in 12 hospitals of Nepal for 18 months. All the women who delivered in the hospitals during the study period was enrolled. Independent researchers collected data on the social and demographic information using semi-structured questionnaire at the time of discharge and clinical events and birth outcome information from the clinical case note. Data were analyzed on the prevalence and type of birth defect. Logistic regression was done to assess the risk factor and consequences for birth defect. Results-Among the total 87,242 livebirths, the prevalence of birth defects was found to be 5.8 per 1000 live births. The commonly occurring birth defects were anencephaly (3.95%), cleft lip (2.77%), cleft lip and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). The odds of birth defect was higher among mothers with age <20 years (adjusted Odds ratio (aOR) 1.64; 95% CI, 1.18-2.28) and disadvantaged ethnicity (aOR 1.78; 95% CI, 1.46-2.18). The odds of birth asphyxia was twice fold higher among babies with birth defect (aOR 1.88; 95% CI, 1.41-2.51) in reference with babies without birth defect. The odds of neonatal infection was twice fold higher among babies with birth defect (aOR 1.82; 95% CI, 1.12-2.96) in reference with babies without birth defect. Babies with birth defect had three-fold risk of pre-discharge mortality (aOR 3.00; 95% CI, 1.93-4.69). Conclusion- Babies with birth defect have high risk for birth asphyxia, neonatal infection and pre-discharge mortality at birth. Further evaluation on the care provided to babies who have birth defect is warranted.

scholarly journals Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength

Development ◽  
2021 ◽  
Vol 148 (19) ◽  
Author(s):  
Jennifer H. Kong ◽  
Cullen B. Young ◽  
Ganesh V. Pusapati ◽  
F. Hernán Espinoza ◽  
Chandni B. Patel ◽  
...  
Keyword(s):  
Small Molecules ◽  
Birth Defects ◽  
Birth Defect ◽  
Hedgehog Signaling ◽  
Multiple Birth ◽  
In Utero Exposure ◽  
Membrane Protein Complex ◽  
Protein Target ◽  
Hh Signaling ◽  
Genetic And Environmental Factors

ABSTRACT Birth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Deficiency of the MMM component MOSMO results in elevated SMO and increased Hh signaling, causing multiple birth defects. In utero exposure to a teratogen that directly inhibits SMO reduces the penetrance and expressivity of birth defects in Mosmo−/− embryos. Additionally, tissues that develop normally in Mosmo−/− embryos are refractory to the teratogen. Thus, changes in the abundance of the protein target of a teratogen can change birth defect outcomes by quantitative shifts in Hh signaling. Consequently, small molecules that re-calibrate signaling strength could be harnessed to rescue structural birth defects.

scholarly journals Demographic Characteristics of Mothers Who Delivered Children with Birth Defetcs

2018 ◽  
pp. 222-227
Author(s):  
Yudianto B Saroyo ◽  
Christian Wijaya ◽  
Putri M T Marsubin
Keyword(s):  
Retrospective Study ◽  
Birth Weight ◽  
Antenatal Care ◽  
Birth Defects ◽  
Medical Records ◽  
Birth Defect ◽  
Demographic Characteristics ◽  
Comorbid Disease ◽  
Increased Risk

Abstract Objective: to determine the characteristics and background of mothers who delivered neonates with birth defects. Methods: A retrospective study was used by evaluating the medical records of patients with birth defects in Dr. Cipto Mangunkusumo Hospital during the period between September 2014 and June 2016. Results: A total of 67 (1.85%) out of 3,619 infants who were born in Dr. Cipto Mangunkusumo Hospital during the period between September 2014 and June 2016 had birth defects. Forty-seven (70.1%) mothers of the subjects irregularly attend antenatal care. The most frequent maternal comorbid disease in this study was asthma, which was found in 4 (5.97%) mothers of the subjects. 48 (58.7%) subjects had birth weight under 2500 g. Conclusion: In this retrospective study, the main highlight is that 70.1% of the mothers who delivered neonates with birth defects did not attend antenatal care regularly. 58.7% of the neonates with birth defects had low birth weight. This study could be used as base for further research investigating about the role of antenatal care in early detection and/or the planning of delivery for babies with birth defects. Trends in babies with birth defects suggested that fetuses diagnosed with IUGR/SGA should be given special attention, as they were at increased risk for birth defects. Keywords: birth defect, maternal description   Abstrak Tujuan: untuk mengetahui deskripsi/ciri-ciri  dan latar belakang ibu yang melahirkan janin dengan kelainan bawaan. Metode: Studi retrospektif digunakan dengan menggunakan data sekunder rekam medis pasien dengan kelainan bawaan di Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo pada periode September 2014-Juni 2016. Hasil: Sejumlah 67 (1.85%) dari 3,619 neonatus didapatkan dengan kelainan bawaan di RSUPN Cipto Mangunkusumo pada periode September 2014-Juni 2016 . Sejumlah 47 (70.1%) ibu dari subjek tidak teratur dalam melakukan kunjungan antenatal care. Penyakit komorbid ibu yang paling banyak ditemukan dalam studi ini adalah asma, yang ditemukan dalam 4 (5.97%) subjek. 48 (58.7%) subyek memiliki berat lahir di bawah 2500 g. Kesimpulan: Pada studi retrospektif ini didapatkan 70.1% ibu yang melahirkan bayi dengan kelainan bawaan tidak melakukan kunjungan antenatal care. Didapatkan bahwa 58,7% bayi yang lahir dengan kelainan bawaan memiliki berat badan lahir rendah (BBLR). Studi ini dapat dijadikan sebagai landasan dilakukannya studi yang lebih besar untuk mengevaluasi peran antenatal care terhadap deteksi dini dan/atau perencanaan persalinan bayi dengan kelainan bawaan. Tren pada bayi dengan kelainan bawaan menunjukkan bahwa janin yang pada antenatal care didapatkan IUGR/SGA patut diperhatikan lebih untuk kecurigaan kemungkinan adanya kelainan bawaan. Kata kunci:   deskripsi ibu,   kelainan bawaan,

LIQUOR INDUSTRY BIRTH DEFECT SUITS

PEDIATRICS ◽  
1989 ◽  
Vol 84 (3) ◽  
pp. A54-A54
Author(s):  
J. F. L.
Keyword(s):  
Birth Defects ◽  
Birth Defect ◽  
Public Attitudes ◽  
Alcoholic Beverage ◽  
Federal District ◽  
District Court ◽  
Fetal Alcohol ◽  
Duty To Warn ◽  
Beverage Industry ◽  
Specific Health

Seattle, April 20—Already faced with declining sales and increasingly hostile public attitudes, the alcoholic beverage industry is bracing for the first in a series of trials in which they are blamed for causing birth defects. The nation's first lawsuit on behalf of children suffering from fetal alcohol syndrome, a birth defect that is the leading known cause of mental retardation, is scheduled to go to trial Monday in Federal District Court here. In the suit, two parents who admit they are alcoholics say a distiller's failure to warn of the link between moderate or heavy whisky consumption and birth defects was the cause of their child's impairment. The suit alleges that liquor manufacturers have a duty to warn consumers that drinking during pregnancy can lead to birth defects. Lawyers for the distiller argue that, because most people already know of the dangers of drinking, the company had no duty to warn of the specific health hazards.

scholarly journals Towards scaling Twitter for digital epidemiology of birth defects

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Ari Z. Klein ◽  
Abeed Sarker ◽  
Davy Weissenbacher ◽  
Graciela Gonzalez-Hernandez
Keyword(s):  
Machine Learning ◽  
Social Media ◽  
Language Processing ◽  
Birth Defects ◽  
Birth Defect ◽  
Learning Algorithms ◽  
Class Imbalance ◽  
Machine Learning Algorithms ◽  
Supervised Machine Learning ◽  
Svm Classifier

Abstract Social media has recently been used to identify and study a small cohort of Twitter users whose pregnancies with birth defect outcomes—the leading cause of infant mortality—could be observed via their publicly available tweets. In this study, we exploit social media on a larger scale by developing natural language processing (NLP) methods to automatically detect, among thousands of users, a cohort of mothers reporting that their child has a birth defect. We used 22,999 annotated tweets to train and evaluate supervised machine learning algorithms—feature-engineered and deep learning-based classifiers—that automatically distinguish tweets referring to the user’s pregnancy outcome from tweets that merely mention birth defects. Because 90% of the tweets merely mention birth defects, we experimented with under-sampling and over-sampling approaches to address this class imbalance. An SVM classifier achieved the best performance for the two positive classes: an F1-score of 0.65 for the “defect” class and 0.51 for the “possible defect” class. We deployed the classifier on 20,457 unlabeled tweets that mention birth defects, which helped identify 542 additional users for potential inclusion in our cohort. Contributions of this study include (1) NLP methods for automatically detecting tweets by users reporting their birth defect outcomes, (2) findings that an SVM classifier can outperform a deep neural network-based classifier for highly imbalanced social media data, (3) evidence that automatic classification can be used to identify additional users for potential inclusion in our cohort, and (4) a publicly available corpus for training and evaluating supervised machine learning algorithms.

Birth defects in the Brazilian side of the triple border: a population-based cross-sectional study

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
F K Nampo ◽  
S Souza ◽  
C R Pestana
Keyword(s):  
Birth Defects ◽  
Birth Defect ◽  
Cleft Lip ◽  
Maternal Education ◽  
Sociodemographic Factors ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Factors Associated ◽  
Major Birth Defect

Abstract Background Major birth defects are characterized by its severity and are a public health challenge since it chronically affects the population. Foz do Iguassu is located in Brazili's largest international border and presents a birth defect rate 50% greater than the country's average. Methods Identifying factors associated to birth defects is important to guide preventive actions toward modifiable risk factors and target the most susceptible population. In this cross-sectional study we measured the prevalence of major birth defects and associated maternal sociodemographic factors in Foz do Iguassu. Data were collected from a governmental registry and included all births that occurred in the city between 2012 to 2017. The variables measured were maternal education, maternal race, country of residence, maternal parity and onset of prenatal care. Data were analyzed through logistic regression models to verify the maternal sociodemographic factors associated with major birth defects. Results 26,214 births were analyzed; among the 305 birth defects registered, 140 (46%) corresponded to a major birth defect. Cleft lip and/or palate and gastroschisis were the most prevalent major birth defect (9.5/10,000 live births and 6.83/10,000 live births, respectively). Maternal education up to 7 years was the only variable associated with the major birth defects (ORadj=1.58; CI = 1.07-2.33; p = 0.02). Maternal age was associated with gastroschisis (mean: 21.5 years; p = 0.002) and Down syndrome (mean: 33.5 years; p = 0.007). Conclusions In this area, cleft lip and/or palate and gastroschisis are the most common major birth defects, and maternal education is weakly associated with major birth defects. Key messages The epidemiology of major birth defects in this area differs from Brazil’s. Future research should focus on inherent risk factors for congenital defects and exposure to teratogens.

scholarly journals Male Sex and the Risk of Childhood Cancer: The Mediating Effect of Birth Defects

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Erin L Marcotte ◽  
Jeremy M Schraw ◽  
Tania A Desrosiers ◽  
Wendy N Nembhard ◽  
Peter H Langlois ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Birth Defects ◽  
Mediation Analysis ◽  
Birth Defect ◽  
Mediating Effect ◽  
Cancer Type ◽  
Increased Risk ◽  
Causal Pathway ◽  
Male Sex ◽  
Risk Of Cancer

Abstract Background There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status. Methods We used a population-based birth cohort with linked data from birth certificates, birth defects registries, and cancer registries from Arkansas, Michigan, North Carolina, and Texas. We conducted counterfactual mediation analysis to estimate the natural direct and indirect effects of sex on cancer risk, modeling birth defect status as mediator. State; birth year; plurality; and maternal race and ethnicity, age, and education were considered confounders. We conducted separate analyses limited to cancers diagnosed younger than 1 year of age. Results Our dataset included 10 181 074 children: 15 110 diagnosed with cancer, 539 567 diagnosed with birth defects, and 2124 co-occurring cases. Birth defect status mediated 38% of the association between sex and cancer overall. The proportion mediated varied by cancer type, including acute myeloid leukemia (93%), neuroblastoma (35%), and non-Hodgkin lymphoma (6%). Among children younger than 1 year of age at cancer diagnosis, the proportion mediated was substantially higher (82%). Conclusions Our results suggest that birth defects mediate a statistically significant proportion of the relationship between sex and childhood cancer. The proportion mediated varied by cancer type and diagnosis age. These findings improve our understanding of the causal pathway underlying male sex as a risk factor for childhood cancer.

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