Human genetics is the study of the inheritance of epigenetic 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 term anthropological 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 than 6,000 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.
- 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.
- 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.
- 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.
- 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.
Heterozygote screening is focused on susceptible populations with high rates of deleterious heterozygosity (for example, cystic fibrosis in Scandinavians, Tay-Sachs in Ashkenazi Jews, sickle cell anemia in Blacks, etc.). Prospective screening of parents, particularly where one is an identified heterozygote, allows more informed medical choices. Pre-symptomatic screening may be helpful within families with a history of Mendelian disorders. Such screening is most typical in certain dominant traits but can be very useful in other types of familial disease risk (for example, cancers of the breast and colon).
Medical genetics also entails other clinical procedures, such as prenatal diagnosis (sampling of chorionic villus tissue, umbilical cord blood, maternal blood sampling, or maternal serum, as well as fetal imaging via ultrasound or radiography). Prenatal screening is especially useful for prospective mothers over age 35 with family history of a condition diagnosed by prenatal tests, to evaluate abnormal maternal serum screening or some complications of pregnancy. Likewise, neonatal screening may be used to identify newborns in need of critical special treatments (special diets for phenylketonuria or replacement therapy for hypothyroidism).
Pedigree analysis is a classical technique of medical genetics by which a thorough family tree is depicted, with symbols for persons affected with known genetic disease. Thus is rendered a broad summary of inheritance patterns through generations that serves to clarify mode of transmission even for traits that may have identical phenotypes despite different causal genes (for example, cleft palate can be Mendelian autosomal dominant, autosomal recessive, or X-linked recessive; other types are multifactorial as they run in families without clear patterns).
However, with this progress, an increasing number of gene tests are becoming available commercially, although the scientific community continues to debate the best way to deliver them to the public and medical communities, who are often unaware of their scientific and social implications. While some of these tests have greatly improved and even saved lives, scientists remain unsure of how to interpret many of them. Also, patients taking the tests face significant risks of jeopardizing their employment or insurance status. And because genetic information is shared, these risks can extend beyond them to their family members as well.
As the role of genetics is made clearer with respect to diagnosis, monitoring, and treatment of diseases, medical scientists continue to make rapid progress in the identification of genes associated with disease. A key long-range aim is to formulate new means to diagnose, treat, and even cure or prevent diseases. Epigenesis is a complex process that entails regulators (i.e., promoters and enhancers), actively expressed units (exons), unexpressed but intervening units (introns), and termination signals.
The field of human genetics has been dramatically bolstered by the Human Genome Project (HGP) and related studies that began in 1991. These constitute the new field of genomics that use techniques of molecular analysis to map all human genes to specific locations and thereby identify elements of genetic structures and functions. With this progress, medical genetics is expanding from a focus on diagnostics and counseling toward more active evaluation and treatment, including the prospect for procedures to directly repair dysgenetic cell lines. Similarly, human genetics has also progressed rapidly toward the elucidation of diverse issues in the phylogenetic history and geography of human populations.
- Cavalli-Sforza, L. L., Menozzi, P., & Piazza, A. (1996). The history and geography of human genes. Princeton, NJ: Princeton University Press.