No AbstractKeywords:Formal genetics; Genetic maps; Structural genomic maps; Functional genomic maps; Experimental genetic map

Salem, MSZ

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The Egyptian Journal of Medical Human Genetics (2014) 15, 99–101Ain Shams UniversityThe Egyptian Journal of Medical Human Geneticswww.ejmhg.eg.netwww.sciencedirect.comEDUCATIONAL CORNER OF THE ISSUEBasic concepts of medical genetics, formal genetics, Part 1Mohammad Saad Zaghloul Salem *Faculty of Medicine, Ain-Shams University, Cairo, EgyptReceived 23 October 2013; accepted 26 October 2013Available online 15 November 2013KEYWORDSFormal genetics;Genetic maps;Structural genomic maps;Functional genomic maps;Experimental genetic maps* Tel.: +20 01225874345/3335E-mail addresses: mszsalem@yPeer review under responsibilitProduction an1110-8630  2014 Productionhttp://dx.doi.org/10.1016/j.ejmh4379.ahoo.comy of Aind hostinand hostig.2013.11. Basic concepts of formal geneticsThe definition of formal genetics is still a matter of contention.However, it can be defined as a branch of basic genetics con-cerned with deducing and figuring out relevant genetic datafrom constructed figures that contain specific genetic informa-tion. These informative figures include, for instance, con-structed family pedigrees, linkage maps and chromosomalmaps. Many aspects of applied and clinical genetics have beenclarified by analysis of information databases collected fromstudies of formal genetics of certain diseases and of specificexperimental researches, e.g. construction of chromosomalmaps of gene loci based on information gathered, formerly,by human–mouse hybridization studies, and currently byin situ hybridization experiments. Progress in disclosing inter-species genetic similarities and dissimilarities, which representmajor targets of research of comparative and evolutionarygenetics, depends largely on species-specific genetic databases, mszsalem@hotmail.comShams University.g by Elsevierng by Elsevier B.V. on behalf of A0.001that are gathered and analyzed within the context of formalgenetics [1]. Although clinical maps composed of pathogno-monic combinations of signs, symptoms and specific patholog-ical findings pointing to specific disease entities represent thesimplest of formal genetic maps, they are not considered,strictly, of formal genetic concern. However, when comparedto, and analyzed with, other informative maps, like linkagemaps and chromosomal maps, clinical maps have major diag-nostic significance in recognition and localization of undefinedgenes underlying, and possibly involved in, pathogenesis ofcertain disorders and malformations.2. Scope of formal geneticsFormal genetics is confined to studying genetic maps, whetherrepresented as figure or text interface data. Relevant aspects offormal genetics pertaining to medical genetics include genea-logical study and analysis of data provided by the family pedi-gree, delineation of classical/traditional/Mendelian and non-classical/non-traditional/non-Mendelian patterns of inheri-tance, construction and analysis of structural and functionalgenomic/transcriptomic/proteomic maps, chromosomal maps,maps of gene loci, linkage maps, association maps, genomicstructural variants (SVs) maps and experimentally inducedand constructed maps, which comprise many types like restric-tion fragment length polymorphism maps, radiation hybridin Shams University.Table 1 Scope and applications of common formal genetic maps.Type of genetic map Relevance to medical genetics1. Family pedigree Genealogical study reveals pattern of inheritance, type of genetic disease,participation of non-genetic factors in pathogenesis of the disease, etc.2. Structural genomic (DNA) maps Provide information on number and distribution of unique genic andunique tandem repeats of non-genic parts or domains of DNA, intergenicregions and repetitive sequences, gene density, etc.3. Functional genomic maps Provide information on distribution of functional genic sequences, non-functional sequences like pseudogenes and duplicated non-functional genes,transposons, pyknons, mutable hot spots of DNA, imprinting centers, etc.4. Genomic structural variants (SVs) maps Reveals human genetic variations and their possible linkage with specifichuman diseases. Also, they are of particular significance in many fields ofstudy of comparative and evolutionary genetics5. Ribonucleic acids (RNA) maps Constituent databases of structure and function of different types of RNA:messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA)and different species of small or microRNAs6. Transcriptome maps Provide databases of (mRNA): structural variations, rates of transcription,of translation and of turnover and decay. Differential characteristicalterations of post-transcription modifications in specific disease states.Comparative analysis of mRNA maps can reveal possible causative genemutations as well as possible underlying pathogenetic mechanisms7. Chromosome maps Reveal details of chromosome topology, e.g. type of chromosome, geneloci, distribution of telomeres and of ribosomal gene repeats, chromatintype and variations, etc.8. Gene maps Clarify the size, base sequence, number of exons and introns, distribution ofhot spots and of CG sites, sequence type and organization of promoterregion of the gene, etc.9. Proteome maps Depict constituent structural and catalytic proteins. Specific proteome mapscan be constructed for specific states, e.g. oncoprotein maps of malignantcells. These can further be classified and delineated according to specifictumor type, e.g. oncoprotein map of hypernephroma, of multiple myeloma,etc.10. Linkage maps Reveal recombination frequency of different types of genetic markers, e.g.genes – traits – proteins – DNA markers, for identifying location of genesrelative to each other on chromosomes, etc.11. Haplotype maps Provide comparative data about inter-individual single nucleotidepolymorphism to determine the likely locations and haplotypes involved inpathogenesis of, or predisposition to, specific diseases, reveal presence andincidence of linkage disequilibrium of certain haplotypes, etc.12. Inter-species hybridization maps Allow for assigning or (mapping) specific genes to specific chromosomesand even to certain chromosome segments13. Restriction fragment length polymorphism (RFLP) maps Used for diagnosis of point mutations that alter a restriction site, and forcomparative purposes, e.g. paternity testing14. Radiation hybrid maps Provide data about relative positions of specific genic and DNA markers onspecific chromosomal regions based on frequency of chromosomalbreakage induced by radiation15. Probe-specific maps Reveal widespread inter-individual as well as inter-species and intra-speciesgenomic and transcriptomic differences, provide critical data forpopulation, comparative, experimental and evolutionary genetic studiesand researches16. Genotype maps Correlate specific genotypes with specific disease states, thus providingcrucial information relevant to provisional clinical diagnosis, effectiveprophylactic management and genetic counseling17. Phenotype maps Depict pathognomonic diagnostic combinations of disease-specific signsand symptoms for genetically-determined and genetically-mediateddisorders100 M.S. Zaghloul SalemBasic concepts of medical genetics, formal genetics, Part 1 101maps, inter-species hybridization maps and probe specificmaps (Table 1). Analysis of formal maps of specific DNAmarkers, which include single nucleotide polymorphism,microsatellite polymorphism and tandem repeat polymor-phism maps, in addition to many others, provide fundamentalinformation crucial for framing better and proper understand-ing of the structure and function(s) of the human genome,transcriptome and proteome [2].3. Formal genetic mapsAs referred to, genetic maps (Table 1) are databases repre-sented as text or graphic interface figures aimed at providingimportant, beneficial and crucial clues relevant to nearly allfields of human genetics including medical genetics [3].4. Applications of formal geneticsThe bioinformatics databases represented as, and includedwithin, different types of formal genetic maps have a wide rangeof applications in many fields of basic, clinical, diagnostic,therapeutic, prophylactic and applied genetics. Constructionof the family pedigree of patients with genetic diseases or offamilies seeking counseling advice, and genealogical analysisof history, clinical and other types of data represented by itsinformative symbols, to derive relevant genetic information,like possible pattern of inheritance, and to calculate recurrencerisk figures in future offspring, constitutes the first step inapproaching patients and families having genetic disorders,and represents the simplest and most direct of these applica-tions [4].Progress in analysis of structural organization of the humangenome generates a flood of information leading to character-ization of new formal maps of specific DNA markers and re-gions of both structural and functional significance. Thesemaps represent bioinformatics databases that can have crucialimpact on many aspects of basic as well as of clinical medicalgenetics. For instance, exome maps comprising detailed infor-mation of exons of genes can be constructed and used for bothintra and inter-species comparative purposes. Similarly, withinthe context of pathogenetics, comparison of exome maps ofpatients with specific idiopathic genetic disorders with thoseof normal subjects represents a revolutionary promising ap-proach that can have many diagnostic applications in clinicalgenetics. Other types of molecular maps that can be con-structed based on available as well as on the rapidly accumu-lating databases of human genome structure, e.g. intromemaps, pyknon maps, transposon maps, telomere maps andmaps of pseudogenes, can also have a wide spectrum of appli-cations in many fields of medical genetics [5].The significant beneficial effects and applications of struc-tural genetic maps in different fields of medical genetics callfor construction of parallel databases of functional geneticmaps that characterize critical functional markers and trans-criptionally active regions and sequences of the human gen-ome. Examples of such functional maps can, possibly,include proteome maps comprising both structural proteinand enzyme, or catalytic, protein databases. Comparativeanalysis of these functional protein maps in normal subjectsand in patients affected with specific genetically-determineddisorders and idiopathic diseases caused by, still, unidentifiedetiological mechanisms, might prove helpful in revealing theunderlying patho-proteomic abnormalities responsible fordevelopment of the specific pathophysiological alterations thatcharacterize the clinical phenotype of each of these diseases. Inaddition, in a way similar to that of reverse engineering, com-parative analysis of normal and abnormal proteome maps ofspecific genetic disorders can disclose underlying pathogeneticmechanisms, patho-transcriptomic differences and causativegenetic mutations possibly involved in mediating the patho-genesis and development of these disorders.References[1] Pierce Benjamin A. Genetics. A conceptual approach. 2nd ed.Gordonsville, VA, USA: W.H. Freeman & company; 2005.[2] Anthony Griffiths JF et al. Introduction to genetic analysis. 9th ed.Gordonsville, VA, USA: W.H. Freeman & company; 2007.[3] Eberhard Passarge. Color atlas of genetics. 3rd ed. Stuttgart, NewYork: Thieme; 2007.[4] Rédei GP. Encyclopedia of genetics, genomics, proteomics andinformatics. 3rd ed. New York, USA: Springer; 2008.[5] Alberts B et al. Molecular biology of the cell. 4th ed. Hamden, CT,USA: Garland Science; 2002.

Basic concepts of medical genetics, formal genetics, Part 1

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Basic concepts of medical genetics, formal genetics, Part 1

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