Genetics, Human

Human genetics is the study of the inheritance of epi-genetic traits among humans, notably but not exclusively traits of medical interest. The overarching goal of human genetics is to apply knowledge of human heredity to a better understanding of diversity in development and adaptation as “nature is nurtured.” Another central goal of human genetics is the public health function of reducing dysgenetic burdens on individuals, families, and society at large. Although the boundaries of subdisiplines within genetics are not precise, the termanthropological genetics is used to distinguish general human genetics from more clinical applications, with the latter sometimes denoted specifically as medical genetics.

Humans, like all species, have many genotypic and phenotypic variations. Such variation is ultimately derived from mutations that affect proteomic expression. Genes encode for proteins that ultimately arrange and regulate all manner of biological structures and processes, from the intracellular level to organismic and even on the ecological. Thus, mutant genes disrupt proper proteomics processes, and disease results to the extent such disruptions are evident as defects (pathophenotypes). Many mutations have no pathological effect, but there are more than6,000 known single-gene disorders, or about 1 of every 200 live births. Moreover, there may be manifold causes of phenotypically similar disease; for example, some 60 congenital forms of deafness are known, with some the result of environmental factors such as rubella and others due to genetic mutations. Genetic disorders, as caused by abnormalities in genetic material, occur in four basic types: (1) single-gene, (2)chromosomal, (3) multifactorial, and (4) mitochondrial.

• 1.
  Single-gene (Mendelian or monogenic) defects are due to mutations of DNA at a single locus. Single-gene diseases arise in the classic familial patterns of inheritance: autosomal dominant, autosomal recessive, and X-linked. Major examples of such Mendelian diseases include cystic fibrosis, sickle cell anemia,Huntington's disease, pheylketonuria, alpha-1-antitrypsin deficiency, and hereditary hemochromatosis.
• 2.
  Chromosomal defects are due to abnormalities such as allelic deletions or redundancies; translocations of or even gross are evident on microscopic examination. Down's syndrome(trisomy 21) is a common disorder that occurs with a redundant portion of chromosome 21.
• 3.
  Multifactorial (complex or polygenic) defects are due to interactions of multiple alleles and the developmental environment. Many of the most common illnesses are multifactorial, including arthritis, cancer, diabetes, heart disease, and hypertension. Given such complexities of expression, multifactorial inheritance is more challenging to study.
• 4.
  Mitochondrial defects are due to mutations in mitochondrial DNA, which is distinct from the inherited nuclear-chromosomal genotype of the organism. Since mitochondria are the small organelles of cellular respiration in the cytoplasm of plant and animal cells, such anomalies can cause a variety of specific metabolic diseases.

Medical genetics historically developed in practical application for medical screening and advice for at-risk populations. Such screening requires not only adequate tests (valid, reliable, sensitive, specific)but also a sound grasp of the natural progression of and treatment options for the disease in question. A thorough family history augmented with a review of pertinent medical literature, preferably by an expert, is essential to inform families of the diagnosis and methods; identification of carriers; the phenomenology of the disorder, including complications; risk of recurrence for the patient and family; and therapeutic and reproductive options, including referral or support groups. This is a complex process of evaluation and education and carries considerable legal and ethic consequences.

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