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Genes
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A gene is the basic unit of heredity. Genes, which are made up of DNA, act as instructions to make the component molecules of the cell.
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Description
In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The genome is all of the genes in a cell's nucleus. The complete genome for a human contains about 3 billion bases and about 20,000 genes on 23 pairs of chromosomes.[1]
Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s individuality. Changes in genes are called mutations; gene mutations can often cause disease.
DNA in the cell has two jobs: 1) to act as instructions in making the component molecules of the cell and 2) to pass on that information to the next generation. DNA itself isn't necessary for a cell to be alive and functional (mature red blood cells, for example, don't have any DNA): the machinery of the cell is made of RNA and proteins. Each DNA sequence that contains instructions to make RNA or protein is known as a gene. The size of a gene may vary greatly, ranging from about 1,000 bases to 1 million bases in humans. Bases are the building blocks of DNA; there are four types (A,T,C,G). Bases are sometimes called nucleotide bases (or nucleotides) or base pairs (because there are two strands of DNA in every chromosome).
Genetics is the study of how genes work and are inherited. Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene’s position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome.
Cytogenetic location
Geneticists use a standardized way of describing a gene’s cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome:
17q12
It can also be written as a range of bands, if less is known about the exact location:
17q12-q21
The combination of numbers and letters provide a gene’s address on a chromosome. This address is made up of several parts:
- The chromosome on which the gene can be found. The first number or letter used to describe a gene’s location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.
- The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene’s address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.
- The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.
Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene’s cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm of chromosome 14. (“Tel” is also sometimes used to describe a gene’s location. “Tel” stands for telomeres, which are at the ends of each chromosome. The abbreviations “tel” and “ter” refer to the same location.)
Molecular location
The Human Genome Project, an international research effort completed in 2003, determined the sequence of base pairs for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of base pairs. For example, the molecular location of the APOE gene on chromosome 19 begins with base pair 50,100,901 and ends with base pair 50,104,488.[2] This range describes the gene’s precise position on chromosome 19 and indicates the size of the gene (3,588 base pairs). Knowing a gene’s molecular location also allows researchers to determine exactly how far the gene is from other genes on the same chromosome.
Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address. For example, the National Center for Biotechnology Information (NCBI) identifies the molecular location of the APOE gene as base pair 50,100,901 to base pair 50,104,488 on chromosome 19. The Ensembl database identifies the location of this gene as base pair 50,100,879 to base pair 50,104,489 on chromosome 19. Neither of these addresses is incorrect; they represent different interpretations of the same data. For consistency, Genetics Home Reference presents data from NCBI for the molecular location of genes.
Gene families
A gene family is a group of genes that share important characteristics. In many cases, genes in a family share a similar sequence of DNA building blocks (nucleotides). These genes provide instructions for making products (such as proteins) that have a similar structure or function. In other cases, dissimilar genes are grouped together in a family because proteins produced from these genes work together as a unit or participate in the same process.
Classifying individual genes into families helps researchers describe how genes are related to each other. Researchers can use gene families to predict the function of newly identified genes based on their similarity to known genes. Similarities among genes in a family can also be used to predict where and when a specific gene is active (expressed). Additionally, gene families may provide clues for identifying genes that are involved in particular diseases.
Sometimes not enough is known about a gene to assign it to an established family. In other cases, genes may fit into more than one family. No formal guidelines define the criteria for grouping genes together. Classification systems for genes continue to evolve as scientists learn more about the structure and function of genes and the relationships between them.
Role of Genes in the Body
Genes contain the instructions for each cell to make proteins and structural RNAs. Proteins are essential for the body to function normally. Proteins are structural components of cells and also enzymes—enzymes perform the chemistry of life; for example, converting sugars to energy and making all of the metabolites (small molecules) in cells. RNA is important for the structure of ribosomes and as intermediaries in the process of making proteins (translation).
How Genes Work
Transcription and translation
Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression.
During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm.
Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a stop codon (a sequence of three bases that does not code for an amino acid).
The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the central dogma.
Through the processes of transcription and translation, information from genes is used to make proteins.
Gene regulation
Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although it is known that the regulation of genes is critical for life, this complex process is not yet fully understood.
Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
Cell division
There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells.
Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result.
The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing.
Control of cell growth and division
A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for mistakes and halt the cycle for repairs if something goes wrong.
If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues.
Inheritance
Each gene in an individual is represented by two copies, called alleles—one on each chromosome pair. There may be more than two alleles, or variants, for a given gene in a population, but only two alleles can be found in an individual. Therefore, the probability that a particular allele will be inherited is 50:50, that is, alleles randomly and independently segregate into daughter cells, although there are some exceptions to this rule.
The term diploid describes a state in which a cell has two sets of homologous chromosomes, or two chromosomes that are the same. The maturation of germ line stem cells into gametes (sperm or egg cells) requires the diploid number of each chromosome be reduced by half. Hence, gametes are said to be haploid—having only a single set of homologous chromosomes. This reduction is accomplished through a process called meiosis, where one chromosome in a diploid pair is sent to each daughter gamete. Human gametes, therefore, contain 23 chromosomes, half the number of somatic cells (the other cells of the body).
Because the chromosome in one pair separates independently of all other chromosomes, each new gamete has the potential for a totally new combination of chromosomes. In humans, the independent segregation of the 23 chromosomes can lead to as many as 16 to 17 million different combinations in one individual's gametes. Only one of these gametes will combine with one of the nearly 17 million possible combinations from the other parent, generating a staggering potential for individual variation. Even more variation is possible because of the recombination between sections of chromosomes during meiosis as well as the random mutation that can occur during DNA replication.
Gene expression
Gene expression, as reflected in an organism's phenotype, is based on conditions specific for each copy of a gene. For every gene there are two copies, and for every gene there can be several variants or alleles. If both alleles are the same, the gene is said to be homozygous. If the alleles are different, they are said to be heterozygous. For some alleles, their influence on phenotype takes precedence over all other alleles. For others, expression depends on whether the gene appears in the homozygous or heterozygous state. Still other phenotypic traits are a combination of several alleles from several different genes. Determining the allelic condition used to be accomplished solely through the analysis of family trees. However, this method can leave many questions unanswered, particularly for traits that are a result of the interaction between several different genes. Today, molecular genetic techniques exist that can assist researchers in tracking the transmission of traits by pinpointing the location of individual genes, identifying allelic variants, and identifying those traits that are caused by multiple genes.
Mendelian
Mendelian refers to the simple expression of genes in the patterns described below. This is based on the observations Gregor Mendel made in his classic pea studies of inheritance.
A dominant allele is an allele that is almost always expressed, even if only one copy is present. Dominant alleles express their phenotype even when paired with a different allele, that is, when heterozygous. In this case, the phenotype appears the same in both the heterozygous and homozygous states. Just how the dominant allele overshadows the other allele depends on the gene, but in some cases the dominant gene produces a gene product that the other allele does not. Well-known dominant alleles occur in the human genes for Huntington disease, a form of dwarfism called achondroplasia, and polydactylism (extra fingers and toes).
On the other hand, a recessive allele will be expressed only if there are two identical copies of that allele, or for a male, if one copy is present on the X chromosome. The phenotype of a recessive allele is only seen when both alleles are the same. When an individual has one dominant allele and one recessive allele, the trait is not expressed because it is overshadowed by the dominant allele. The individual is said to be a carrier for that trait. Examples of recessive disorders in humans include sickle cell anemia, Tay-Sachs disease, and phenylketonuria (PKU).
A particularly important category of genetic linkage has to do with the X and Y sex chromosomes. These chromosomes not only carry the genes that determine male and female traits, but also those for some other characteristics as well. Genes that are carried by either sex chromosome are said to be sex linked. Men normally have an X and a Y combination of sex chromosomes, whereas women have two X's. Because only men inherit Y chromosomes, they are the only ones to inherit Y-linked traits. Both men and women can have X-linked traits because both inherit X chromosomes.
X-linked traits not related to feminine body characteristics are primarily expressed in the phenotype of men. This is because men have only one X chromosome. Subsequently, genes on that chromosome that do not code for gender are expressed in the male phenotype, even if they are recessive. In women, a recessive allele on one X chromosome is often masked in their phenotype by a dominant normal allele on the other. This explains why women are frequently carriers of X-linked traits but more rarely have them expressed in their own phenotypes. In humans, at least 320 genes are X-linked. These include the genes for hemophilia, red–green color blindness, and congenital night blindness. There are at least a dozen Y-linked genes, in addition to those that code for masculine physical traits.
Exceptions
Pleiotropism, or pleotrophy, refers to the phenomenon in which a single gene is responsible for producing multiple, distinct, and apparently unrelated phenotypic traits; that is, an individual can exhibit many different phenotypic outcomes. This is because the gene product is active in many places in the body. An example is Marfan syndrome, where there is a defect in the gene coding for a connective tissue protein. Individuals with Marfan syndrome exhibit abnormalities in their eyes, skeletal system, and cardiovascular system.
Some genes mask the expression of other genes just as a fully dominant allele masks the expression of its recessive counterpart. A gene that masks the phenotypic effect of another gene is called an epistatic gene; the gene it subordinates is the hypostatic gene. The gene for albinism in humans is an epistatic gene. It is not part of the interacting skin-color genes. Rather, its dominant allele is necessary for the development of any skin pigment, and its recessive homozygous state results in the albino condition, regardless of how many other pigment genes may be present. Because of the effects of an epistatic gene, some individuals who inherit the dominant, disease-causing gene show only partial symptoms of the disease. Some, in fact, may show no expression of the disease-causing gene, a condition referred to as nonpenetrance. The individual in whom such a nonpenetrant mutant gene exists will be phenotypically normal but still capable of passing the deleterious gene on to offspring, who may exhibit the full-blown disease.
There are also traits that are multigenic, that is, they result from the expression of several different genes. This is true for human eye color, in which at least three different genes are responsible for determining eye color. A brown/blue gene and a central brown gene are both found on chromosome 15, whereas a green/blue gene is found on chromosome 19. The interaction between these genes is not well understood. It is speculated that there may be other genes that control other factors, such as the amount of pigment deposited in the iris. This multigenic system explains why two blue-eyed individuals can have a brown-eyed child.
Somatic mosaicism causes conditions such as having two different colored eyes. Every cell in an adult is ultimately derived from the single-cell fertilized egg. Therefore, every cell in the adult normally carries the same genetic information. However, if a mutation occurs in only one cell at the two-cell stage of development, the adult is composed of two types of cells: cells with the mutation and cells without. If a mutation affecting melanin production occurs in one of the cells in the cell lineage of one eye but not the other, then the eyes would have different genetic potential for melanin synthesis. This could produce eyes of two different colors.
Penetrance refers to the degree to which a particular allele is expressed in a population phenotype. If every individual carrying a dominant mutant gene demonstrates the mutant phenotype, the gene is said to show complete penetrance.
Diseases of the Genes
Many diseases occur as a result of problems with genes.
Cancer
Cancer results from a disruption of the normal regulation of the cell cycle. When the cycle proceeds without control, cells can divide without order and accumulate genetic defects that can lead to a cancerous tumor. Cancer can be thought of as uncontrolled cell division by tumor cells.
Gene mutations
There are two places where mutations can be introduced and carried into the next generation. In the first stages of development, a sperm cell and egg cell fuse. They then begin to divide, giving rise to cells that differentiate into tissue-specific cell types. One early type of differentiated cell is the germ line cell, which may ultimately develop into mature gametes. If a mutation occurs in the developing germ line cell, it may persist until that individual reaches reproductive age. Now the mutation has the potential to be passed on to the next generation.
Mutations may also be introduced during meiosis, the mode of cell replication for the formation of sperm and egg cells. In this case, the germ line cell is healthy, and the mutation is introduced during the actual process of gamete replication. Once again, the sperm or egg will contain the mutation, and during the reproductive process, this mutation may then be passed on to the offspring.
Not all mutations are bad. Mutations also provide a species with the opportunity to adapt to new environments, as well as to protect a species from new pathogens. Mutations are what lie behind the popular saying of "survival of the fittest," the basic theory of evolution proposed by Charles Darwin in 1859. This theory proposes that as new environments arise, individuals carrying certain mutations that enable an evolutionary advantage will survive to pass this mutation on to its offspring. It does not suggest that a mutation is derived from the environment, but that survival in that environment is enhanced by a particular mutation. Some genes, and even some organisms, have evolved to tolerate mutations better than others. For example, some viral genes are known to have high mutation rates. Mutations serve the virus well by enabling adaptive traits, such as changes in the outer protein coat so that it can escape detection and thereby destruction by the host's immune system. Viruses also produce certain enzymes that are necessary for infection of a host cell. A mutation within such an enzyme may result in a new form that still allows the virus to infect its host but that is no longer blocked by an anti-viral drug. This will allow the virus to propagate freely in its environment.
The gene mutations entry has a more detailed discussion of the diseases associated with mutations.
Inheritance
Many gene abnormalities are responsible for genetic problems that are passed in families. These are classified by inheritance pattern, described above.
Dominant
Recessive
X-linked
Pleiotropic
Epistatic
Related Professions
- Geneticists provide counseling and evaluation for individuals with genetic diseases.
History
How genes were discovered
The modern science of genetics traces its roots to Gregor Mendel, a scientist who studied of the nature of inheritance in plants. In 1866, he studied the transmission of seven different pea traits by carefully test-crossing many distinct varieties of peas. Mendel's simple approach led to fundamental insights into genetic inheritance, known today as Mendel's Laws. Mendel did not actually know or understand the cellular mechanisms that produced the results he observed. Nonetheless, he correctly surmised the behavior of traits and the mathematical predictions of their transmission, the independent segregation of alleles during gamete production, and the independent assortment of genes. Mendel's work was largely ignored by the scientific community for over 30 years.
How genes were named
In 1909, Danish botanist Wilhelm Johanssen coined the word gene for the hereditary unit found on a chromosome. Nearly 50 years earlier, Gregor Mendel had characterized hereditary units as factors. The word's roots are traced to German genesis.[3]
Research
The Human Genome Project was completed in 2003. Analyses of the data obtained in this project are ongoing.
References
- ↑ National Human Genome Research Institute Web site. Deoxyribonucleic Acid (DNA).
- ↑ Genetics Home Reference Web site. Genes: APOE.
- ↑ Merriam-Webster Online. Gene.
External Links
Genetics Home Reference: A service of the U.S. National Library of Medicine.
National Human Genome Research Institute
National Center for Biotechnology Information
The New Genetics: A free publication of the National Institute of General Medical Sciences discussing the history, present use, and future of genetics.
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The content on or accessible through Medpedia.com is for informational purposes only. Medpedia is not a substitute for professional advice or expert medical services from a qualified health professional.
Read more
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