Genetics
Objectives- Define: genome, chromosome, gene, allele, intron, exon, codon, haploid, diploid, mutation, homeobox gene, transcription, translation, receptor, recombinant protein, karyotype, genotype, phenotype, penetrance, variable expressivity, anticipation, pleitropy
- Define the process by which genetic material is transferred from the nucleus to the synthesized protein
A basic knowledge of the terminology of molecular biology and genetics is essential to the orthopaedist's ability to understand many of the conditions seen in children. As the genome project progresses toward its scheduled completion in 2003, an immense new body of knowledge is unfolding. It is not unreasonable to expect that this knowledge will dramatically change many longheld concepts of children's orthopaedic conditions. We already have a better understanding of many connective tissue disorders, and classification is becoming more logical based on genetic information (for example, Ehlers-Danlos syndrome has recently been reclassified in this manner). Thus, the orthopaedist must have the basic vocabulary to understand the ever-expanding knowledge base in this field.
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• Genome -the total DNA in an organism. In humans, the 23
chromosome pairs contain 80,000-100,000 genes, and a total of 6 billion
base pairs (bonding the double helix of DNA)
• Chromosome -single DNA molecule containing hereditary information
• Gene -a group of base pairs in the chromosome whose sequence provides the information necessary for cells to synthesize a particular structural protein or enzyme (one gene -one protein)
• Allele -alternate forms of a specific gene, may be maternal or paternal. If alleles are identical, organism is homozygous
• Intron -noncoding portion of DNA. Contains promoter regions, regulatory elements, and enhancers. Comprises the majority of DNA
• Exon -contain the code for the RNA of the transcribed template that will be used to produce the protein of the gene product
• Codon -a 3 nucleotide sequence on DNA determining the formation of a specific amino acid
• Diploid -cells with 2 sets of genetic material, one from each parent
• Haploid -genetic material from a single parent (gamete)
• Mutation -a permanent change, deletion, insertion, or rearrangement of base pairs bonding DNA helices.
• Homeobox gene -establishes a molecular coordinate system that determines body design and arrangement
• Transcription -transfer of genetic code from DNA to RNA. Exons are spliced together, introns are spliced out during this process which creates functional messenger RNA
• Translation -process by which messenger RNA transports the code for a protein amino acid sequence from the nucleus to the site of cytoplasmic synthesis
• Receptor -in the plasma membrane of cells, receptors bind with growth factor, hormones, or other proteins to induce a change in cellular behavior
• Recombinant protein -the product of manipulation of segments of DNA and/ or RNA; the selected segments are recombined with other portions of genetic material and then introduced into the genome of an organism or cell to produce a recombinant protein
• Karyotype -the complement of chromosomes for an organism. For humans, this contains 22 pairs of autosomes, and one pair of sex chromosomes
• Genotype -genetic constitution at one or more loci
• Phenotype -the detectable expression of the genotype
• Penetrance -the probability that the phenotype will express the genotype
• Variable expressitivity -different severities of phenotypic expression of the same genotype
• Anticipation -worsening of phenotype in successive generations
• Pleiotropy -diverse phenotypic manifestations of a single gene disorder
It is by this process that mutations involving a single gene can have such a widespread effect. The best clinical example is evident in most forms of osteogenesis imperfecta. A variety of point mutations in the COLIA1 and COLIA2 genes result in transmission of genetic information producing faulty collagen with diminished mechanical strength.
References
- Cole W. Genes and orthopaedics. J Bone Joint Surg( Br) 1999; 81-B: 190-92.
- Jaffurs D, Evans CH. The human genome project: Implications for the treatment of musculoskeletal disease. J Am Acad Ortho Surg 1998; 6: 1-14.
- Rosier RN, Reynolds PR, O' Keefe RJ. Molecular and cell biology in orthopaedics. In: Buckwalter JA, Einhorn TA, Simon SR, editors. Orthopaedic Basic Science. Biology and Biomechanics of the Musculoskeletal System. 2 ed: American Academy of Orthpaeic Surgeons; 2000. p. 20-76.
- Shore EM, Kaplan FS. Tutorial: Molecular biology for the clinician: Part I. General principles. Clin Orthop 1995; 306: 264-83.
- Shore EM, Kaplan FS. Tutorial: Molecular biology for the clinician: Part II. Tools of molecular biology. Clin Orthop 1995; 320: 247-78.
May 16-19, 2012 in Denver, CO
