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Human
Genetics Principles by James L. Weber,
Ph.D.
Our bodies are comprised of trillions of microscopic units called cells. Cells in turn are built up from many specific types of molecules, both large and small. The large molecules or macromolecules include polysaccharides, nucleic acids and proteins. Proteins are the workhorses of our cells:
There are about 30,000
different types of proteins in our bodies. Each protein is present
in many, many copies. An adult, for example, carries about 1021
(a billion trillion) hemoglobin molecules. Hemoglobin is the protein
in our blood which ferries oxygen from the lungs to the rest of
our body.
Each protein is a linear polymer of a specific sequence of 20 different amino acids. DNA is also a linear polymer comprised of 4 types of nucleotides. The sequence of amino acids in each protein is encoded by a segment of DNA called a gene. Three consecutive nucleotides in a gene encode a single amino acid in the corresponding protein. The genetic code is universal among all living things. Each human life begins with a single, microscopic cell. This single cell contains no bones, liver, brain, or any other adult tissue, but does contain a full complement of genetic instructions (genes) to specify all these tissues. In this very real sense, our genome is a blueprint for people. The genetic blueprint encodes the sequences of all the proteins within our bodies and also programs human development for all stages of our lives from the single cell to old age. DNA is a double helical molecule with specific base pairing rules. Each of the two strands of the double helical structure serves as a template for synthesis of a new DNA strand during replication. Before a cell divides, the DNA within the cell nucleus is copied with exceptional fidelity. Each of the two daughter cells receives an identical copy of the DNA instructions. The sum total of DNA within an organism is the organism’s genome. The human haploid genome (one copy of each chromosome) contains about 3 billion nucleotides. Each chromosome contains a single very long DNA molecule. Each of the approximately 30,000 genes within our genome is located at a precise position along one of the chromosomes. The Human Genome Project is the organized, international effort to map and sequence the entire human genome. Much information about the human genome including maps and sequences are available through the internet. The great majority of the human DNA sequence has now been determined. DNA is an exceptionally ancient and stable molecule. It is passed from one generation to the next with only very gradual change. The nucleotide sequences of chimpanzee (our closest living relative) and human DNA are about 98.5% identical despite the fact that our last common ancestor lived about 6 million years ago. Similarities in DNA nucleotide sequences can be detected between all free living organisms including reptiles and plants, worms and fungi, and humans and bacteria. The degree of similarity in DNA nucleotide sequences from two species indicates the evolutionary relatedness of the two species. Humans have 46 total chromosomes, two copies of each of 23 different types. Chromosomes 1 through 22 are the same in both males and females. The sex (X and Y) chromosomes differ between the sexes. Males have one X and one Y chromosome, whereas females have two X and no Y chromosomes. One copy of each chromosome type is inherited from the mother and one from the father. A father contributes an X chromosome to each of his daughters and a Y chromosome to each of his sons. Each pair of homologous human chromosomes, whether from a single individual or from two individuals are about 99.9% identical in sequence. This is why all humans from all parts of the planet are so much alike, and so different from all other animals including even our closest living relatives. Nevertheless, with 3 billion total nucleotides, 0.1% difference means about 3 million nucleotide differences among homologous chromosomes. These DNA sequence differences are largely, but not entirely, responsible for the differences among people. Some human traits and diseases are completely heritable, some partially heritable, and some are not influenced by genes at all. Examples of traits and disorders in each category are shown below. Traits and disorders are established to be heritable by family studies, twin studies and animal studies. Not all human traits have been examined for heritability. Traits and disorders which are partially heritable are also influenced by nongenetic or environmental factors. As examples, diet influences height, and cigarette smoking influences lung cancer. Completely (or nearly completely) heritable:
Partially heritable:
Not (or only very weakly) heritable:
Human diseases are inherited through dominant, recessive and complex modes. Dominant inheritance means one copy of the abnormal gene is sufficient to cause disease. Examples of dominant disorders include Huntington’s disease, some forms of breast cancer and some forms of Alzheimer’s disease. Recessive inheritance means two abnormal copies of the relevant gene must be present in the affected individual. Examples of recessive disorders include cystic fibrosis, sickle cell anemia and many forms of deafness. When an abnormal gene responsible for a recessive disorder is located on the X chromosome, then only males are primarily affected. Examples of such "sex-linked" recessive disorders are hemophilia and color blindness. Complex inheritance often means that several genes combine to influence a single trait or disease and that nongenetic factors also play a role. Through the genome project and through other studies, scientists are learning which nucleotide sequence differences influence specific disorders and traits. Today, we know relatively few of the genetic variations which affect common human traits and disorders. However, many scientists are working on this problem, and our catalogue of such variants is growing rapidly. Along with this knowledge has come the technology necessary to efficiently screen for DNA variations. Using a small of amount of blood or other tissue from a donor, laboratory experts can now readily determine the nucleotide sequence of virtually any segment of human DNA. Our fantastic new ability to screen human DNA sequences has the potential to provide great benefit or great harm. Many tough ethical, legal, and social questions are raised by our new genetic technologies. We will wrestle with these tough issues all of our lives. The more people understand genetics, the better prepared they will be to deal with these issues. Genetics education is therefore critical to effectively applying this powerful new knowledge and technology. |