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B Modell

Publications and source records attributed to B Modell.

At least 37 records · Page 2Linked to original sources
PubMed1998

The history of community genetics: the contribution of the haemoglobin disorders.

The emerging possibilities of applying new diagnostic technologies for genetic diagnosis and screening point to the need for a discipline of community genetics. Genetic population screening for haemoglobin disorders (thalassaemias and sickle cell disorders) has been practised on a large scale for over 20 years, and basic concepts and methods of community genetics have been developed within this framework, under the auspices of the WHO. Genetic population screening is a public health activity. It involves many disciplines, and planning depends on reliable and regularly updated information. Basic methods for describing genetic epidemiology in terms of service needs, and for regular service audit have been developed, and IT-based approaches for making simple, accurate and diagnosis-specific information accessible to the public and health professionals are being explored.

Journal Article↗
PubMed1997

Audit of prenatal diagnosis for haemoglobin disorders in the United Kingdom: the first 20 years.

OBJECTIVES: To audit services for prenatal diagnosis for haemoglobin disorders in the United Kingdom. DESIGN: Comparison of the annual number of cases recorded in a United Kingdom register of prenatal diagnoses for haemoglobin disorders, with the annual number of pregnancies at risk of these disorders, by ethnic group and regional health authority. The number of pregnancies at risk was estimated using data on ethnic group from the 1991 census and data from the United Kingdom thalassaemia register, which records the number of babies born with thalassaemia. SETTING: The three national prenatal diagnosis centres for haemoglobin disorders. SUBJECTS: 2068 cases of prenatal diagnosis for haemoglobin disorders in the United Kingdom from 1974 to 1994. MAIN OUTCOME MEASURES: Utilisation of prenatal diagnosis by risk, ethnic group, and regional health authority. Proportion of referrals in the first trimester and before the birth of any affected child. RESULTS: National utilisation of prenatal diagnosis for haemoglobin disorders was around 20%. During the past 10 years it has remained steady at about 50% for thalassaemias and risen from 7% to 13% for sickle cell disorders. Utilisation for sickle cell disorders varies regionally from 2% to 20%. Utilisation for thalassaemias varies by ethnic group. It is almost 90% for Cypriots and ranges regionally for British Pakistanis from 0% to over 60%. About 60% of first prenatal diagnoses are done for couples without an affected child. Less than 50% of first referrals are in the first trimester. CONCLUSIONS: National utilisation of prenatal diagnosis for haemoglobin disorders is far lower than expected, and there are wide regional variations. A high proportion of referrals are still in the second trimester and after the birth of an affected child. The findings point to serious shortcomings in present antenatal screening practice and in local screening policies and to inadequate counselling resources, especially for British Pakistanis.

Africa↗
PubMed1997

The Baigas of Madhya Pradesh: a demographic study.

This paper outlines the demographic characteristics of the Baiga tribe, one of the most primitive of the aboriginal tribal groups of Central India. The Baiga population has grown steadily since the first anthropological study of the tribe in the 1930s. Age at menarche, age at marriage, breast-feeding, and time interval between marriage and first conception are natural. There are more females than males. Sub-tribe endogamy is common; consanguineous marriage is favoured (34% of marriages are between first cousins) and marital distance is low (mean 7.1 km). Though the mean menarcheal age is high (15.2 years), mean age at first marriage is low (16.6 years), giving a long reproductive period.

Adolescent↗
PubMed1997

Relationship between the severity of beta-thalassaemia syndromes and the number of alleviating mutations.

Thalassaemia intermedia, defined as homozygous beta-thalassaemia in which patients are not transfusion-dependent, covers a wide range of clinical severity. It may arise because one or more genetic factors ameliorate the otherwise severe phenotype of thalassaemia major. Exactly which and how many such mutations are necessary to produce a thalassaemia intermedia phenotype is incompletely understood, although such information would be useful both clinically and for prenatal diagnosis. We examined DNA from 28 patients with thalassaemia intermedia resident in London and 28 matched patients with thalassaemia major, for 3 types of genetic modifying factors, namely; mild beta-thalassaemia mutations, the upstream XmnI G-gamma globin gene polymorphism, and alpha-globin gene deletions. The results show that the number of alleviating mutations present has a large influence on the phenotype of patients with homozygous beta-thalassaemias. A single alleviating mutation was present in 56% of thalassaemia intermedia subjects compared with 26% of thalassaemia major subjects. Two alleviating mutations were present in 33% of thalassaemia intermedia subjects compared with 1 thalassaemia major subject. No patients with thalassaemia major had 3 alleviating mutations, in contrast to 11% of those with thalassaemia intermedia. Although the findings did not account for the full range of phenotypic variation, such information is of potential value both in the clinical management and the prenatal diagnosis of homozygous beta-thalassaemia.

Adolescent↗
PubMed1997

Delivering genetic screening to the community.

Concern is often expressed that, in the future, screening for genetic risk will become too widespread. Haemoglobin disorders (the thalassaemias and sickle cell disorders) offer an excellent model for genetic screening, because they are common and severe. They are recessively inherited. Carriers can be detected by conventional blood tests with an accuracy of 99%, so couples at risk can be identified before they have children and offered genetic counselling and prenatal diagnosis. Carrier-screening programmes have been in place in several countries for over 20 years and now offer extensive practical experience of the problems of delivering the service equitably to entire populations. This experience suggests that the main risk is of too little rather than too much genetic screening, and of doing it badly, and demonstrates the need for a discipline of 'community genetics'. Here I propose that modern information technology has a central role in providing communities with adequate access to correct genetic information.

Anemia, Sickle Cell↗
PubMed1996

Reproductive behaviour and natural selection for the sickle gene in the Baiga tribe of central India: the role of social parenting.

We have investigated the transmission of the sickle cell gene in relation to tribal structure, and genetic fitness in a primitive Indian tribal population, the Baiga. Factors operating on gene frequency include protection of AS individuals against falciparum malaria, a high frequency of genetic factors capable of moderating the severity of sickle cell anaemia (alpha-thalassaemia and Xmn I polymorphism in G gamma gene), a high frequency of consanguineous marriage, and reproductive compensation by couples at risk for sickle cell anaemia. The study incidentally made it possible to measure the extent of "social parenting' in such a tribal society for the first time: deviation from expectation in the distribution of the Hb A and S genes within families suggests that up to 30% of children may not be offspring of their ostensible parents.

Anemia, Sickle Cell↗
PubMed1995

Prenatal screening for haemoglobin disorders.

The technology has been available to detect carriers of haemoglobin disorders since the late 1960s. Prenatal diagnosis has been available since 1978. First trimester diagnosis by chorionic villus sampling and DNA analysis was introduced in 1982, and subsequent simplifications in DNA technology have made screening, counselling and prenatal diagnosis cost-effective at the community level, in countries at all levels of development. Audit of prenatal diagnosis for haemoglobin disorders in countries which have the resources and infrastructure necessary for genetic population screening (such as the UK and other European countries), has shown that the number of prenatal diagnoses actually performed fall far short of expectation. The demonstration that this reflects failures in delivering information, screening and counselling to the populations at risk, rather than rejection of prenatal diagnosis, shows the importance of placing more emphasis on the organisational and social requirements for genetic population screening. In some countries current attitudes towards abortion exclude provision of prenatal diagnosis within the health service, but in many such cases it has been set up in the private sector. It is also being introduced through combined private and charitable efforts in an increasing number of developing countries, including some with extremely limited health resources: such centres are likely to act as nuclei for emergence of genetics services in these communities. A particularly notable recent achievement is the introduction of prenatal diagnosis in Nigeria, where 1-2% of all children born suffer from sickling disorders.

Developing Countries↗
PubMed1995

Hereditary anaemias and iron deficiency in a tribal population (the Baiga) of central India.

We have studied the prevalence and molecular nature of hereditary anaemias (abnormal haemoglobins, beta-thalassaemia, alpha-thalassaemia, and Glucose 6 phosphate dehydrogenase (G6PD) deficiency) in a primitive central Indian tribe, the Baiga. 43% of the population appear to be iron-deficient. Hereditary anaemia gene frequencies are, sickle cell 0.0824, G6PD deficiency (in males) 0.0457, beta-thalassaemia 0.0057, and deletional alpha-plus thalassaemia 0.65. Both -alpha 3.7 and -alpha 4.2 deletions were observed and non-deletional alpha-thalassaemia was suspected. The overall gene frequency of Xmn I+polymorphism (C-->T - 158 cap site; upstream of G gamma region) is 0.35. This polymorphism is preferentially linked to beta s genes. It appears that sickle cell disease covers a wide range of severity in the Baiga tribe based on higher mortality in the offspring of AS x AS parents (2.5/couple) compared to AA x AS (0.75/couple) and AA x AA (0.76/couple) parents. This is compatible with the high frequency of genetic modifying factors, i.e., the Xmn I polymorphism and alpha-thalassaemia. The results also indicate that "normal" red cell values must be defined for each population where thalassaemias, G6PD deficiency and iron deficiency are common.

Anemia↗
PubMed1995

Psychosocial and clinical burden of thalassaemia intermedia and its implications for prenatal diagnosis.

Twenty eight patients with thalassaemia intermedia and their parents were interviewed using specifically designed questionnaires to evaluate psychosocial burden. Hospital notes were analysed for clinical burden. A wide variation was found for both patients and parents, ranging from virtually unaffected to severely affected. Normal sexual function and setting up a family were mentioned by patients and parents as being particularly important for quality of life. Over half (58%) of the patients had problems with sexual maturation and functioning, and continuous monitoring of all patients with thalassaemia intermedia by a paediatric endocrinologist is therefore strongly indicated. Most parents said, in light of their experiences, that they would opt for prenatal diagnosis and termination of affected pregnancies even if a genotype predicting the mild form of disorder were discovered.

Abortion, Legal↗
PubMed1995

Prevention and control of haemoglobinopathies.

In many developing countries the haemoglobinopathies (thalassaemias and sickle-cell disorder) are so common that they provide a convenient model for working out a genetic approach to control of chronic childhood diseases. At present, about 250 million people (4.5% of the world population) carry a potentially pathological haemoglobinopathy gene. Each year about 300,000 infants are born with major haemoglobinopathies. Haemoglobinopathy control programmes, based on WHO approaches and recommendations, have been established in different countries in all WHO Regions and have been successful in management of the problem. Following WHO recommendations the health burden of hereditary anaemias could be significantly reduced. This article summarizes the presentations and discussion made at a joint WHO/TIF (Thalassaemia International Federation) meeting, held in Cyprus in April 1993, and reviews the experience of programmes in several countries for the control of haemoglobinopathies in the world.

Global Health↗
PubMed1994

Thalassaemia in Azerbaijan.

beta thalassaemia is present throughout the southern regions of the former USSR. We have defined the clinical picture of the disorder, the spectrum of beta thalassaemia mutations, and the role of customary consanguineous marriage in Azerbaijan, where thalassaemia presents a public health problem of the same order as that in Greece. Contrary to earlier suggestions, we found that the common form of the disorder is typically severe. Typical Turkish, Mediterranean, Azeri, Kurdish, and Asian Indian mutations were found, consistent with the history of the region. The common Mediterranean beta 0 thalassaemia mutation (codon 39) was not found. Three mutations (codon 8-AA, IVS2-1 and IVS1-110) account for over 80% of beta thalassaemia genes. Consanguineous marriage appears to contribute relatively little to the frequency of affected births. These observations provide the basis for a thalassaemia prevention programme in Azerbaijan.

Adolescent↗
PubMed1993

What proportion of congenital abnormalities can be prevented?

OBJECTIVE: To estimate the proportion of preventable congenital abnormalities in Hungary. DESIGN: Analysis of available Hungarian data-bases and of the effectiveness of primary, secondary, and tertiary preventive methods. SETTING: Databases of ad hoc epidemiological studies and of the Hungarian congenital abnormality registry. MAIN OUTCOME MEASURES: Prevalence at birth and prevalence after prevention in 73 congenital abnormality types or groups. RESULTS: Preventive methods are available for 51 (70%) of the 73 congenital abnormality types or groups evaluated. The birth prevalence of all congenital abnormalities could be reduced from 65 to 26 per 1000; thus 39 per 1000 (60%) are preventable. Without congenital dislocation of the hip, which is unusually common in Hungary, the preventable proportion of congenital abnormalities is 52%. CONCLUSION: Many congenital abnormalities can be prevented, but as they do not represent a single pathological category there is no single strategy for their prevention.

Abnormalities, Multiple↗
PubMed1993

A scientific basis for cost-benefit analysis of genetics services.

Economic appraisal of genetics services is important, but, in this sensitive area, analyses limited to financial aspects understandably cause public concern. Evaluation of these services must take account of their aim of helping everyone with a genetic disadvantage to live and reproduce as normally as possible, and must apply equally to patients and to couples at risk of having affected children. Here we propose that the classical concept of genetic fitness can be useful in evaluating genetics services, because it is measurable, and truly represents their underlying aim.

Abortion, Therapeutic↗