The Human Genome And Genetic Disorders:

This Chapter was written following fruitful discussions with my colleague, Erik Niebuhr, MD, DSc, University of Copenhagen.

Study Objectives

· To define allele, anaphase, anticodon, autosomes, chromatid, chromatin, chromosome, clone, codon, diploid, exons, gene, gene frequency, haploid, haemophilia, introns, nucleotides, post-translational modification, probability, promoter sequence, ribosomal translation, sex-linked genes, splicing, transcription, translocation, and transversion.

· To describe the human genome, gene therapy, and the roles of DNA, RNA, messenger RNA, transfer RNA and recombinant DNA

· To calculate the frequency of abnormal genes in the total gene pool of a population.

· To explain protein synthesis, DNA transcription, mutations, and genetic disorders.

· To use the above concepts in problem solving and case histories.

Principles

· Many hormones regulate genes expressed by some cells. This mechanism controls the synthesis of enzymes, receptor proteins, structural proteins, and transcription proteins. This is why steroid and thyroid hormones require hours for their biological effect.

· The partial or total lack of specificity in the third base of some triplet codons may allow 2-4 codons, differing only in the third base, to code for the same amino acid.

Definitions

· Allele is an alternative form of a gene occupying the same locus on a particular chromosome.

· Anaphase refers to the stage of nuclear division, which is characterized by movement of chromosomes from spindle equator to spindle pools.

· Anticodon is the group of three nucleotides in transfer RNA that pairs complementarily with three nucleotides of messenger RNA during protein synthesis.

· Autosomes refers to any chromosome which is not a sex chromosome or mitochondrial chromosome. Humans possess 22 pairs of autosomes.

· Bacteriophag is a bacterial virus. Bacterial viruses are modified and used as vectors for DNA cloning.

· Chromatid results from the replication of chromosomes during interphase. A chromatid is one of the two identical halves of a chromosome, which shares a common centromere with a sister chromatid.

· Chromatin refers to the nuclear material, which comprises the chromosomes: The DNA complex.

· Chromosomes are nucleoprotein structures, which are the sites of nuclear genes arranged in linear order.

· Clone. A group of cells or organisms derived from a single ancestral cell or individual by asexual multiplication (repeated mitoses). All members of a clone are genetically identical.

· Codon or triplet code is determined by a base triple (three adjacent nucleotides that code for one amino acid). A codon encodes a specific amino acid residue to be added into the peptide chain or specifies termination of translation. Three codons in mRNA (UAA, UAG and UGA) are stop codons. The signals encoded by the codons form the genetic code.

· Dalton refers to a weight unit equal to the mass of the hydrogen atom.

· Deoxyribonucleic acid (DNA) is a helical coiled nucleic acid molecule composed of deoxyribose-phosphate units connected by paired bases attached to the deoxyribose sugar. DNA is the genetic material of all living organisms and vira.

· Diploid refers to the number of chromosomes found in somatic cells (ie, two sets).

· DNA polymerase is the enzyme that replicates DNA.

· Dominant describes a trait expressed in individuals who are heterozygous for a particular gene

· Exon is a segment of a gene that is represented in the final spliced mRNA product.

· Expressivity is the degree to which the effect of a gene is expressed.

· Frequency refers to the relative number of actual cases per 100 000 persons in a population.

· Gene is a part of a DNA molecule that codes for the synthesis of a specific polypeptide chain through its sequence of nucleotides. Each human gene extends over 40 kb in general, but we also posses longer genes. The gene, located in the chromosome, is the particulate determiner of hereditary trait.

· Gene frequency refers to the number of loci at which a gene occurs, divided by the number of loci at which it could occur. This is the proportion of one allele of a pair of genes present in the population.

· Gene therapy is the application of gene transfer (DNA delivery to cells) in an attempt to treat genetic or acquired disorders. The transferred DNA must contain promoter zones for transcription and the protein-coding region of the gene.

· Genome is the total amount of genetic material in the cell.

· Genotype is the genetic constitution of an individual.

· Haploid refers to an individual or germ cell having a single complete set of chromosomes (one set).

· Heterozygote is an individual possessing two different alleles at the corresponding loci on a pair of homologous chromosomes.

· Homozygote is an individual possessing identical alleles at the corresponding loci on a pair of homologous chromosomes.

· Haemophilia is an X-linked, recessive genetic disorder characterised by free bleeding from even slight wounds because of lack of formation of clotting substance.

· Incidence refers to the new cases of a disorder diagnosed per year in a population group.

· Intron is a segment of a gene not represented in the final mRNA product. The segment ha