Malaria

Malaria provides the classic example of an infectious disease exerting an evolutionary pressure on humans so that protective mutations in genes are maintained in the populations who live in malaria endemic areas. Once the close geographical correlation of the prevalences of malaria and red blood cell disorders (hemoglobinopathies) was noted, Haldane proposed, in the late 1940s, that they might be protective against severe malaria (Haldane, 1949). Only a few years later Allison published the...

Prohormone convertase 1 deficiency

Further evidence for the role of the melanocortin system in the regulation of body weight in humans comes from the description of a 47-year-old woman with severe childhood obesity, abnormal glucose homeostasis, very low plasma insulin but elevated levels of proinsulin, hypogonadotropic hypogonadism and hypocortisolemia associated with elevated levels of POMC (O'Rahilly et al., 1995). This subject was found to be a compound heterozygote for mutations in prohormone conver-tase 1, which cleaves...

Diseases of genomic imprinting

Mammals possess an epigenetic system thought to be important for fetus-mother nutrient transfer and normal development, termed genomic imprinting (Constancia et al., 2002 Ferguson-Smith et al., 2003b Ferguson-Smith et al., 2004 Reik et al., 2003 Walter and Paulsen, 2003). Epigenetic guidelines are imprints laid down in germ cells (in most cases by DNA methyltransferases) governing how genes are expressed depending on their parental origin, be it maternal or paternal (Bjornsson et al., 2004...

Is achieving extreme old age worthwhile the centenarian phenotype

Average life expectancy has markedly increased over the past century. In 1900 average life expectancy was 46 years and in the United States it is currently almost 79 years. The age 85+ group is the fastest growing segment of our population and within that group, the number of centenarians is growing even faster. Whether mortality declines have been accompanied by health improvements among the elderly has been a matter of debate. Some authors have suggested that mortality declines have led to...

Current applications of pharmacogenetics

Our knowledge of pharmacogenetics can be applied in two main areas - (a) in improving the use of existing commonly prescribed drugs and (b) in the development and use of new drugs by the pharmaceutical and biotechnology industries. a) Current drugs The ability to individualize the use of currently used drugs will not only permit the identification of individuals vulnerable to drug side effects but, perhaps more importantly, will allow us to identify those patients who will or will not respond...

Bardet Biedl syndrome

Bardet-Biedl syndrome (BBS) is a rare (prevalence < 1 100000), autosomal recessive disease characterized by obesity, mental retardation, dysmorphic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism and structural abnormalities of the kidney or functional renal impairment (Katsanis et al., 2001b). Bardet-Biedl syndrome is a genetically heterogeneous disorder that is now known to map to at least eight loci 11q13 (BBS1) (Mykytyn et...

Hardy Weinberg and genetic drift

A ''locus'' is broadly defined in population genetics as a single genetic unit. It can be a single nucleotide site or a single contiguous region of a chromosome. The most basic model of polymorphism (genetic variation) in population genetics is a single locus with two alleles A and a, at frequencies p and q respectively, where p + q 1. The first - and simplest - prediction of population genetics was described independently in 1908 by a British mathematician, G. H. Hardy, and a German...

Allelic heterogeneity at Mendelian loci

The loci that underlie Mendelian traits often exhibit extensive allelic heterogeneity (Terwilliger and Weiss, 1998 Estivill et al., 1997). That is, there are often many different independent mutations at a single locus that cause disease. We now describe a simple population genetic model to understand allelic heterogeneity at such loci, and then briefly describe the extensions that have been used to predict what patterns of allelic heterogeneity are like at complex disease loci. Consider a...

Noninsulindependent Type II diabetes mellitus

The incidence of non-insulin-dependent (i.e. Type II) diabetes mellitus (NIDDM) is increasing in adult urban populations around the world. The approximately 3 of adults currently affected by NIDDM will become an estimated 5 by 2025 (World Health Organization, 1998), as populations age and urbanize, and as obesity becomes more prevalent. NIDDM is a serious metabolic disorder which damages kidneys, heart, blood vessels and retina. The disorder results from ''insulin resistance'' - a reduction in...

Lessons from maturity onset diabetes of the young MODY

As mentioned earlier, a small proportion (around 1 ) of families with diabetes are clearly segregating an autosomal dominant form of early-onset T2D (Frayling et al., 2001). The term ''maturity onset diabetes of the young'' (MODY) was coined to describe these key clinical features, at a time when most diabetes seen before late middle age was autoimmune (that is, type 1, or juvenile-onset diabetes as it was then known). Most people with MODY were not particularly obese, suggesting that the...

The structure and mechanism of amyloid formation

Studies of amyloid fibrils formed by both disease-associated and other peptides and proteins has enabled many of the features of these structures to be defined Fandrich and Dobson, 2002 Lopez De La Paz et al., 2002 Selkoe, 2003 Serpell et al., 2000 Wille et al., 2002 , although no complete structure has yet been determined in atomic detail. It is clear that the core structure of the fibrils is stabilized primarily by interactions, particularly hydrogen bonds, involving the atoms of the extended...