P1: SBT9780521850063c12CUUS128/Nicholl978 0 521 85006 3March 11, 200813:30Chapter 12 summaryAimsrTo outline the impact of gene manipulation in medicine and forensic sciencerTo describe the form and patterns of inheritance for some genetically based diseasesrTo evaluate the potential of gene therapy and RNA interference in therapeuticsrTo describe the use of gene manipulation technology in an investigative contextChapter summary/learning outcomesWhen you have completed this chapter you will have knowledge of:rThe diagnosis and characterisation of medical conditionsrThe main patterns of inheritance of genetic conditionsrGenetically based diseasesrGene therapyrRNA interference and its potential in therapeutic applicationsrDNA profiling and its applications in the analysis of genomesKey wordsCongenital, aetiology, human immunodeficiency virus (HIV), acquired immune deficiency syndrome(AIDS), enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay, Western blot, indirectimmunofluorescence assay (IFA), false negative, tuberculosis, human papilloma virus, Lyme disease,diploid, autosomes, sex chromosomes, haploid, gametes, meiosis, zygote, monogenic, polygenic,alleles, dominant, recessive, homozygous, heterozygous, autosomal dominant, autosomal recessive,X-linked, maternal pattern of inheritance, penetrance, expressivity, incomplete penetrance, variableexpressivity, multiple alleles, incomplete dominance, co-dominance, partial dominance,multifactorial, Online Mendelian Inheritance in Man (OMIM), chromosomal abnormalities(aberrations), gene mutations, ploidy number, triploid, tetraploid, aneuploidy, monosomic, trisomic,Down syndrome, non-disjunction, gene mutations, cystic fibrosis (CF), pancreatic exocrinedeficiency, cystic fibrosis transmembrane conductance regulator (CFTR), positional cloning,chromosome walking, chromosome jumping, phenylalanine, allele-specific oligoonucleotides (ASOs),Huntington disease (HD), trinucleotide repeat, muscular dystrophy (MD), Duchenne musculardystrophy (DMD), Becker muscular dystrophy (BMD), dystrophin, transgene, gene therapy, somaticcell, germ line cell, gene replacement therapy, gene addition therapy, antisense mRNA, ex vivo genetherapy, in vivo gene therapy, vehicle, retrovirus, adenovirus, adeno-associated virus, liposome,lipoplex, adenosine deaminase deficiency, severe combined immunodeficiency syndrome, enzymereplacement therapy, animal model, ornithine transcarbamylase deficiency, X-linked severecombined immunodeficiency syndrome, enhancement gene therapy, RNA interference (RNAi),down-regulation, knockdown, gene silencing, post-transcriptional gene silencing, dicer, slicer, shortinterfering RNAs (siRNAs), RNA induced silencing complex (RISC), micro RNAs (miRNAs), age-relatedmacular degeneration (AMD), macula, vascular endothelial growth factor, monozygotic twins, DNAfingerprinting, DNA profiling, minisatellite, variable number tandem repeat (VNTR), multi-locusprobe, single-locus probe, short tandem repeat (STR), microsatellite, European Network of ForensicScience Institutes, Combined DNA Index System, molecular paleontology, molecular ecology.226P1: SBT9780521850063c12CUUS128/Nicholl978 0 521 85006 3March 11, 200813:30Chapter 12Medical and forensicapplications of genemanipulationThe diagnosis and treatment of human disease is one area in whichgenetic manipulation is beginning to have a considerable effect. Asoutlined in Chapter 11, many therapeutic proteins are now madeby recombinant DNA (rDNA) methods, and the number available isincreasing steadily. Thus, the treatment of conditions by recombinant-derived products is already well established. In this chapter we willlook at how the techniques of gene manipulation impact moredirectly on medical diagnosis and treatment, and we will also exam-ine the use of rDNA technology in forensic science. Recent progressin both of these areas is of course closely linked to our increasingknowledge of the human genome, and new developments in medicaland forensic applications will undoubtedly appear as we continue todecipher the genome.12.1 Diagnosis and characterisationof medical conditionsGenetically based diseases (often called simply genetic diseases) rep-resent one of the most important classes of disease, particularly inchildren. A disorder present at birth is termed a congenital abnor-mality, and around 5% of newborn babies will suffer from a seriousmedical problem of this type. In most of these cases there will be asignificant genetic component in the aetiology (cause) of the disease.It is estimated that about a third of primary admissions to paediatrichospitals are due to genetically based problems, whilst some 70% ofcases presenting more than once are due to genetic defects. In addi-tion to genetic problems appearing at birth or in childhood, it seemsthat a large proportion of diseases presenting in later life also havea genetic cause or predisposition. Thus, medical genetics, in its tradi-tional non-recombinant form, has alr