Organization of the Human Genome
From WikiGenetics
Understanding the underlying concepts of human genetics and the role of genes, behavior, and the environment will be important to appropriately collecting and applying genetic information and technologies during clinical care. This chapter provides some fundamental information about basic genetic concepts including cell structure, the molecular and biochemical basis of disease, major types of genetic disease, laws of inheritance, and the impact of genetic variation.
Almost every human trait and disease has a genetic component, whether inherited or by modifying the body’s response to environmental factors such as toxins or behavioral factors such as exercise. Understanding the underlying concepts of human genetics and the interactive role of genes, behavior, and the environment will be important in improving disease diagnosis and treatment. This section presents a broad overview of concepts in basic genetics and the molecular and biochemical basis of disease.
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[edit] Cells, Genomes, DNA and Genes
Cells are the fundamental working units of every living system. All the instructions needed to direct their activities are contained within a DNA (deoxyribonucleic acid) sequence. DNA from all organisms is made up of the same chemical units (base pairs) abbreviated as A, T, C, and G. The human genome (total composition of genetic material within a cell) is packaged into larger units known as chromosomes—physically separate molecules that range in length from about 50 million to 250 million base pairs. Human cells contain two sets of chromosomes, one set inherited from each parent. Each cell, except sperm and eggs, contains 23 pairs of chromosomes which consist of 22 autosomes (numbered 1 through 22) and one pair of sex chromosomes (XX or XY). Sperm and eggs contain half as much genetic material (in other words, only one copy of each chromosome).
Each chromosome contains many genes, the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions for how to make proteins. The DNA sequence is the particular side-by-side arrangement of bases along the DNA strand (e.g., ATTCCGGA). Each gene has a unique DNA sequence. The human genome is estimated to contain 20,000-25,000 genes. Genes comprise only about 29 percent of the human genome; the remainder consists of non-coding regions, whose functions may include providing chromosomal structural integrity and regulating where, when, and in what quantity proteins are made.
Although each cell contains a full complement of DNA, different cell types have some genes "turned on" (active) and others "turned off" (inactive). For example, the genes active in a liver cell differ from genes active in a brain cell; as a result, the proteins produced by these cells also differ. Genes are generally activated during development, but also may respond to environmental stimuli such as an infection or stress. Cancer cells typically represent cells that have lost their normal controls and produce primarily proteins involved in cell replication.
[edit] Genetic Variation
All individuals are 99.9 percent the same with respect to their DNA sequence. Differences in the sequence of DNA among individuals are called genetic variation. Genetic variation explains some of the differences among people, such as physical traits and whether a person has a higher or lower risk for certain diseases. Variations in genetic sequence may affect single nucleotides; these are known as single nucleotide polymorphisms (SNPs). SNPs occur every 100 to 300 bases along the 3-billion-base human genome. A single individual may carry millions of SNPs. SNPs can be analyzed to determine whether an individual differs from another--as in DNA identity tests--or whether a particular variation is associated with a particular condition or disease--as in genome-wide anaysis.
Geneticists consider all variations in DNA as mutations, but not all variations are "bad" mutations. For example, variations in a single gene account for the different blood types A, B, AB and O. Because each individual has two genes for blood type--one from mother and one from father--and each gene is active in producing a specific protein, we can tell from blood types that an individual with type AB blood has both the A variant and the B variant in her DNA. An individual with O blood has neither. A person with A blood type has either two A genes or one A and one O; a similar situation is true of the B blood type. These variations are not considered related to a disease or detrimental condition, but should be considered before pregnancies involving parents with different blood types.
However, a single nucleotide variation in the hemoglobin gene--which is responsible for production of the protein that carries oxygen through the body--is responsible for the condition known as sickle cell anemia. Individuals with two copies of the variant gene have anemia; those with one "normal" and one variant ("mutant") gene are carriers for the condition, and can pass it on to offspring, but are not themselves affected. Although the mutation (variation) in this case appears to be "bad", individuals who have the variant gene are better able to handle malaria. So, a mutation that appears "bad" in one situation may be "good" in another.
Understanding the clinical significance of genetic variation is a complicated process because of our limited knowledge of which genes are involved in a disease or condition, and the multiple gene-gene and gene-behavior-environment interactions likely to be involved in complex, chronic diseases. New technologies are enabling faster and more accurate detection of genetic variants in hundreds or thousands of genes in a single experiment.
NCHPEG-Principles of Genetics for Health Professionals for important medical principles in human genetics.
[edit] References
Genetic Alliance. 2007. Understanding Genetics: A Guide for Patients and Health Care Professionals. http://www.geneticalliance.org/ws_display.asp?filter=understanding.genetics.download
[edit] See Also
- Genes and Their Properties
- Inheritance
- Chromosomes in Cells
- Mutations: Changes in the Genome
- Variation
[edit] External Links
Department of Energy, Human Genome Project Education Resources. http://www.ornl.gov/sci/techresources/Human_Genome/education/education.shtml
National Library of Medicine, Genetics Home Reference–Your Guide to Understanding Genetic Conditions. http://ghr.nlm.nih.gov/
Online Mendelian Inheritance in Man. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
