Alan Holland Bittles

• PhD ScD FRCPath
• Professor (Associate) at Murdoch University

The Government of India is presently engaged in the implementation of a prevention and control programme for two major forms of haemoglobinopathies, thalassaemia major and sickle cell disease, with guidelines for their prevention and management formulated under the National Health Mission. Based on projections for the population up to the year 2026...

To an extent the question posed in the title of this paper can simply be answered in the affirmative. Based on the extensive data available from the National Family Health Survey-1 (NFHS-1) conducted in 1992–93 and NFHS-4 in 2015–16 there has been a significant overall decline of some 19% in the prevalence of consanguineous marriage in India. Howev...

The effects of marriage between biological relatives on the incidence of childhood genetic illness and mortality are of major policy significance, as rates of consanguinity exceed 50% in various countries. Empirical research on this question is complicated by the fact that consanguinity is often correlated with poverty and other unobserved characte...

As a single species, all humans are genetically related to some degree. Differences in the levels of homozygosity in the progeny of random mating couples by comparison with those who practice assortative mating, endogamy, and consanguinity are therefore largely quantitative. In earlier generations, positive assortative mating, including marriage wi...

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and prematur...

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However...

The study aimed to explore with consanguineous couples in Australia the acceptability and perceived utility of whole exome reproductive carrier screening for autosomal recessive and X-linked recessive conditions. Semi-structured interviews with 21 consanguineous couples were conducted prior to the offer of screening. Interviews were coded, and them...

Human populations can be divided into societies in which marriage between close family members is traditional and societies where it is avoided or precluded. Consanguineous unions are mainly chosen on cultural, social, and economic grounds, whereas the reasons for their avoidance largely reflect religious doctrine and the prevention of adverse heal...

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and prematur...

Purpose: To provide proof of concept by broadening preconception screening beyond targeted testing to inform reproductive risk in consanguineous couples. Methods: Consanguineous couples were screened for autosomal recessive and X-linked disorders using the TruSight One panel of 4,813 genes associated with human disease. Results: We recruited 2...

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of...

Key features of the Rare Disease Registry Framework (RDRF).

Background Congenital anomalies (CAs) are a common cause of infant death and disability. We linked children from a large birth cohort to a routine primary care database to detect CA diagnoses from birth to age 5 years. There could be evidence of underreporting by CA registries as they estimate that only 2% of CA registrations occur after age 1 year...

Congenital disorders are an important cause of pregnancy loss, premature death and life-long disability. A range of interventions can greatly reduce their burden, but the absence of local epidemiological data on their prevalence and the impact of interventions impede policy and service development in many countries. In an attempt to overcome these...

Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these impor...

When registries collect accurate clinical data over time, they can act as fundamental support structures for patients and their families and powerful cost-effective instruments to support clinical trials and translational research to improve quality of care, quality of life and survival. Registries are critical for rare diseases (RD) with low preva...

In high income countries the life expectancy of people with Down syndrome (DS) rose significantly during the 20th century, from around nine years in 1949 to 57 years by 2000, equating to an increase of approximately 1 year of age per calendar year. This presentation quantifies survival patterns for people with DS using comprehensive population-base...

Orphan drug clinical trials often are adversely affected by a lack of high quality treatment efficacy data that can be reliably compared across large patient cohorts derived from multiple governmental and country jurisdictions. It is critical that these patient data be captured with limited corporate involvement. For some time, there have been call...

The biraderi (brotherhood) is a long-established, widely prevalent dimension of social stratification in Pakistani communities worldwide. Alongside consanguinity, it offers a route for cementing social solidarities and so has strong socio-biological significance. A detailed breakdown of biraderi affiliation among participants in an ongoing birth co...

Purpose: This study investigated two of the stresses experienced by parents caring for offspring with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in Western Australia, and identified their coping strategies. Methods: Parents of 19 offspring with AS and PWS participated in the Family Stress and Coping Interview which provides a stress...

Consanguineous marriage is a controversial topic in many Western societies, with attention mainly focused on the health of immigrant communities from Asia and Africa. In the UK consanguinity is especially prevalent in the Pakistani community, which now numbers over 1.1 million. Less attention has been paid to the influence of hereditary population...

INCREASING PREVALENCE OF CONSANGUINEOUS MARRIAGE CONFIRMED IN KHYBER PAKHTUNKHWA PROVINCE, PAKISTAN - Volume 48 Issue 3 - Aftab Alam Sthanadar, Alan H. Bittles, Muhammad Zahid

RESPONSE TO REHMAN ET AL. (2015) - Volume 48 Issue 3 - Aftab Alam Sthanadar, Alan H. Bittles, Muhammad Zahid

The global human population can be divided into societies in which legal marriage between close family members traditionally has been favored and practiced, and those in which it is avoided or precluded. Consanguineous unions are mainly chosen on social and economic grounds, whereas the reasons for their avoidance are based on religious teachings a...

OBJECTIVE Aim of the present study was to assess the risk of major anomalies in the offspring of consanguineous couples, including data of the prenatal situation.METHODS Over 20 years (1993-2012), 35,391 fetuses were examined by prenatal sonography. In 675 cases (1.9%) parents were consanguineous, with 307 couples (45.5%) related as first cousins,...

T he purpose of this first chapter is to provide readers with background information on consanguineous marriage that is essential for contextualizing the issues discussed in the individual case studies presented across the three parts of this book. After defining consanguineous marriage from a medical genetics perspective, the chapter goes on to de...

Background. Consanguineous marriage is strongly favored in many regions of the world, despite the prevalent Western belief that the progeny of close kin unions experience developmental disorders and premature mortality. Objective. We outline an alternative perspective on the association between consanguinity and disease, in terms of life history th...

Summary. Information on the current prevalence and types of consanguineous marriages in Malakand District, Khyber Pakhtunkhwa Province (KPK), Pakistan, was collected from 1192 rural couples. Some 66.4% of marriages were between couples related as second cousins or closer (Fb0.0156), equivalent to a mean coefficient of inbreeding (a) of 0.0338. The...

Rare Disease registries have now been recognized as a global priority for progress in monitoring, documenting the natural course, preventing and treating Rare Diseases. However, a disease registry is only one element of Rare Disease translational research. Here, we outline what we believe are ten key components in comprehensive Rare Disease transla...

Objectives: The aims of the study were to determine the prevalence, types and socio-economic correlates of consanguineous marriages in Iran, and to gauge the extent to which consanguinity influenced fertility, pregnancy outcomes and the expression of genetic disorders in the present-day population. Methods: Data on the prevalence of consanguinit...

Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally rare lysosomal storage disease caused by a deficiency of arylsulfatase B. However, in Monte Santo, a poor and isolated rural region in Northeast Brazil with large family sizes and high rates of community endogamy and parental consanguinity (α = 0.00483), 9 living and 4 n...

Information on the current prevalence and types of consanguineous marriages in Malakand District, Khyber Paktunkhwa Province (KPK), Pakistan was collected from 1,192 rural couples. Some 66.4% of marriages were between couples related as second cousins or closer, equivalent to a mean coefficient of inbreeding of 0.0338. The data suggest that the pre...

Objective: There are many hearing impaired individuals in Monte Santo, a rural municipality in the state of Bahia, Brazil, including multiple familial cases strongly suggestive of a genetic aetiology. Methods: The present study investigated 81 subjects with hearing impairment (HI) recruited from 36 families. Mutations often associated with HI, i...

Background: Major increases in the survival of people with Down syndrome during the last two generations have resulted in extended periods of adulthood requiring specialist care, which in turn necessitates greater understanding of the nature, timing and impact of comorbidities associated with the disorder. Method: The prevalence of five comorbid...

During the course of the last decade there has been extensive discussion on the role of genetics and genomics in global healthcare, with major diagnostic advances regularly announced, such as exome sequencing to identify and classify de novo, autosomal and X-linked mutations in people with severe intellectual disability,1 and whole-genome sequencin...

Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million. Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services...

Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-...

Significant differences of protein expression profiles between male and female in different age groups. (DOC)

Comparisons of protein expression profiles among the different age groups. (DOC)

Consanguineous unions have been associated with an increased susceptibility to various forms of inherited disease. Although consanguinity is known to contribute to recessive diseases, the potential role of consanguinity in certain common birth defects is less clear, particularly since the disease pathophysiology may involve genetic and environmenta...

An essential guide to this major contemporary issue, Consanguinity in Context is a uniquely comprehensive account of intra-familial marriage. Detailed information on past and present religious, social, and legal practices and prohibitions is presented as a backdrop to the preferences and beliefs of the 1100+ million people in consanguineous unions....

Web-based informatics resources for genetic disorders have evolved from genome-wide databases like OMIM and HGMD to Locus Specific databases (LSDBs) and National and Ethnic Mutation Databases (NEMDBs). However, with the increasing amenability of genetic disorders to diagnosis and better management, many previously underreported conditions are emerg...

Numerous articles have been published linking consanguineous marriage to an elevated prevalence of congenital heart disease, with ventricular septal defects and atrial septal defects the most commonly cited disorders. While initially persuasive, on closer examination many of these studies have fundamental shortcomings in their design and in the rec...

Approximately 1.1 billion people currently live in countries where consanguineous marriages are customary, and among them one in every three marriages is between cousins. Opinions diverge between those warning of the possible health risks to offspring and others who highlight the social benefits of consanguineous marriages. A consanguinity study gr...

Most studies on consanguinity have been conducted on contemporary populations and have focused on the prevalence and types of preferred intra-familial marriage. With its comprehensive birth, marriage and deaths records dating back to the late 17th century, and the legal bar on first cousin marriage removed in the mid-19th century, Sweden offers uni...

To examine the determinants of semen quality in a large sample of military personnel from different geographical areas of the People's Republic of China. Cross-sectional study. Six representative geographical regions in China: Beihai, Lhasa, Germu, Xinzhou, Huhehaote, and Mohe. 1,194 army personnel aged 18 to 35 years at the time of their inclusion...

No abstract available.

Marriage between biological relatives is widely popular in many parts of the world, with over 1000 million people living in countries where 20-50+% of unions are contracted between couples related as second cousins or closer. Consanguinity is, however, a controversial topic, in part due to public misunderstanding, complicated by often exaggerated p...

Mate choice among early human groups and in many historical populations was subject to both demographic and social constraints, ensuring that most unions were between couples who had coinherited substantial proportions of their genomes from common ancestors. Even in populations in which close consanguineous marriage was proscribed, community endoga...

Thalassaemia is a common and debilitating autosomal recessive disorder affecting many populations in South Asia. To date, efforts to create a regional profile of β-thalassaemia mutations have largely concentrated on the populations of India. The present study updates and expands an earlier profile of β-thalassaemia mutations in India, and incorpora...

Arabs are a Semitic people basically defined as individuals speaking Arabic as their native tongue, although with many different dialects, who self-identify as being of Arab ancestry. The Arab world extends from Iraq and the Gulf States in the east to Morocco and Mauritania on the Atlantic coast of North Africa in the west, and through time it has...

This paper presents a definition of the medical field of community genetics. It starts with a brief historical overview, defines the requirements for an adequate definition, presents the definition, and discusses the constituent parts of the definition.

There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or close...

The health and survival of people with intellectual and developmental disabilities (IDD) have increased significantly during the past century, aided by deinstitutionalisation and improved access to health care. In high-income countries, life expectancy estimates are now approximately 70 years for people with mild IDD and 60 years for those with mor...

In western countries, consanguineous marriage often arouses curiosity and prejudice in approximately equally measure, despite the fact that until the mid-nineteenth century cousin marriages were quite common in Europe and North America. Attitudes to consanguinity remain very different in other parts of the world, in particular north and sub-Saharan...

Unlabelled: Thalassaemia and sickle cell disease have been recognized by the World Health Organization as important inherited disorders principally impacting on the populations of low income countries. To create a national and regional profile of β-thalassaemia mutations in the population of India, a meta-analysis was conducted on 17 selected stud...

There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or close...

A major transition in human population structure is currently under way, moving from a historical metapopulation, comprising small and mainly rural endogamous communities, to large and increasingly panmictic urban populations. This process is predicted to increase outbreeding, and preliminary data from genomic surveys have helped to quantify the po...

A survey of the genetic ancestry of 125 Cambodian children resident in Siem Reap province was undertaken, based on eight Y-chromosome binary polymorphisms and sequencing of the mtDNA HV1 region. The data indicated a largely East Asian paternal ancestry and a local Southeast Asian maternal ancestry. The presence of Y-chromosomes P* and R1al* was sug...

Australia has a multicultural society that has arisen from continuing migration. While the population is relatively small, just over 20.7 million, it is genetically diverse and is spread over a large land mass. The federal system of government is democratic, based on states and territories, and there is a socialized healthcare system, in which publ...

A major transition in human population structure is currently under way, moving from a historical metapopulation, comprising small and mainly rural endogamous communities, to large and increasingly panmictic urban populations. This process is predicted to increase outbreeding, and preliminary data from genomic surveys have helped to quantify the po...

Although old age is readily recognizable, methods to define and measure the underlying biological processes are much less amenable to study. For this reason, life expectancy has been widely used as a surrogate measure of ageing, as well as to monitor economic progress at national and regional levels. It is generally acknowledged that lifespan is a...

Arab societies are characterized by a wide range of family and social structures, religious and legal conventions, and highly variable economic resources. As might be expected under these circumstances, genetic services cannot readily be devised, delivered, and assessed according to a single model. However, in general terms, the provision of geneti...

Marriage between close biological kin is widely regarded as genetically disadvantageous in contemporary Western societies, but consanguineous unions remain preferential in North Africa, the Middle East and large parts of Asia, with marriage between first cousins particularly popular. Many major populations also are subdivided into endogamous commun...

Consanguineous marriage has long been a controversial topic, with particular attention focused on adverse health outcomes. Unfortunately, the studies that have been conducted on consanguinity to date have usually lacked control for important sociodemographic variables, such as maternal age and birth intervals, and in estimating specific disease gen...

Remarkably few studies have been conducted into the prevalence and possible influence of close kin marriage on fertility and mortality in northern European populations. The Demographic DataBase at Umeå University offers a unique opportunity to correct this situation, with data on births, deaths, and marriages in the Skellefteå region of Sweden for...

In the countries of Western Europe, death rates declined rapidly during the 20th century, resulting in present-day life expectancies that range from 75–79 years for males and 80–84 years for females. Premature mortality among people with intellectual and developmental disability (IDD) also decreased very significantly, especially over the course of...

With the advent of genomic analysis, increasingly sophisticated statistical methods have been devised to investigate and characterize human population structure. Coalescent theory allows the allelic states of individuals to be generated by assigning an allelic state to their most common recent ancestor (MRCA), with their lines of descent either fol...

Down syndrome (DS) affects approximately 1 per 650-1000 live births and is the most common known genetic cause of intellectual disability. A highly significant change in the survival of people with DS has occurred during the last two generations, with life expectancy estimates increasing from 12 to nearly 60 years of age. Subjects and Detailed info...

Initial physical anthropology studies into ethnic diversity were largely dependent on comparative whole body and craniometric measurements, and through time assessments of ethnic diversity based on these measures exhibited increasing statistical sophistication. Since the 1990s, in Asia as elsewhere in the world, human diversity studies have increas...

Down syndrome is one of the commonest causes of intellectual disability. As life expectancy improves with early and more intensive surgical and medical treatments, people with the disorder are more likely to exhibit classic morbidity and mortality patterns and be diagnosed with diseases such as cancer. A profile of cancer cases among people with Do...

Blood counts, hemoglobin (Hb) high performance liquid chromatography (HPLC), and DNA analyses were performed on 260 children, aged 5 months to 16 years, at Siem Reap to assess the prevalence of thalassemia and other hemoglobinopathies in regional Cambodia. Hemoglobinopathies were present in 134 children (51.5%) with 20 abnormal genotypes identified...