MUTATIONS. Mutagens. Point mutations substitutions. Mutations. Sickle-cell disease. Point mutations insertions & deletions
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1 MUTTIONS Mutgens Mutgens re physicl or chemicl gents tht give rise to muttions. High energy rdition UV, X, gmm. se nlogues, intercltors, chemicl chnge inducers. ffect DN structure, se piring, etc iology Olympid Preprtion Progrm 2 Spontneous muttions rise from errors in DN repliction, repir, recomintion iology Olympid Preprtion Progrm 3 Muttions Muttions re chnges in the genetic mteril of cell. They re importnt for evolution the ultimte source of new genes. Muttions in germ line cells cn e pssed onto offspring. Muttions in other somtic cells re not hereditry. 2 rod types Point muttions Chromosoml muttions 2004 iology Olympid Preprtion Progrm 4 Point muttions sustitutions Replcement of one se pir with nother pir of nucleotides. Silent muttion no chnge due to redundncy of genetic code. Missense muttion chnge. Nonsense muttion stop codon cretion from nucleotide sustitution iology Olympid Preprtion Progrm 5 Point muttions insertions & deletions dditions or losses of se pirs in gene. Often disstrous frmeshift muttions. Sickle-cell disese Point muttion sustitution, cusing missense. Frmeshift cusing extensive missense. Frmeshift cusing immedite nonsense. No extensive frmeshift iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 7 1
2 Chromosoml muttions ltertions of chromosome numer ltered chromosome numer neuploidy Polyploidy Nondisjunction occurs where chromosomes or chromtids do not seprte properly during telophse of meiosis. ltered chromosome structure Dughter cells receive norml numers of chromosomes iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 9 neuploidy Down syndrome trisomy 21. neuploidy rises when n norml gmete with n+1 or n-1 chromosomes is fertilised with norml gmete. Trisomic cells hve 2n+1 chromosomes. Monosomic cells hve 2n-1 chromosomes. Polyploidy Polyploidy is where more thn 2 complete sets of chromosomes re present in cell. 3 sets is triploid, 4 sets is tetrploid, etc. Norml is 2 sets, diploid. Common in plnts whet is hexploid! 2004 iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 11 ltertions of chromosome structure Deletions remove chromosoml segments. Duplictions repet chromosoml segments. Inversions invert chromosoml segments. Trnsloctions move segments etween nonhomologous chromosomes. Often reciprocl. Muttions, in summry Mutgens re physicl or chemicl gents tht cuse muttions. Spontneous muttions rise from errors in DN repliction, repir nd recomintion. Muttions re chnges in the genetic mkeup of cells. They cn e inherited if found in germ line cells. Muttions re the ultimte source of genetic vrition on which evolution cts. Point muttions re chnges in one se pir of gene nd include sustitutions, insertions nd deletions. Frmeshift muttions my result from insertions nd deletions. neuploidy nd polyploidy re ltertions in chromosome numer nd cn e cused y nondisjunction during meiosis iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 13 2
3 MENDELIN GENETICS Gregor Mendel s pes Mendel trnsferred pollen from one flower of one plnt (eg white) to crpel of nother (eg purple). Mendel lwys knew the prentge of new seeds. Thousnds of replictes; chose the right chrcters to study iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 15 Chrcters, trits nd genertions Chrcters heritle fetures. Trits vritions of chrcters. ll offspring of true-reeding prents re of the sme vriety s ech other nd the prents. P genertion is hyridized. Hyrid offspring of P genertion is F 1 genertion. F 2 genertion rises from self-pollintion of F 1 genertion iology Olympid Preprtion Progrm 16 lleles Homozygous individuls hve pir of identicl lleles for chrcter. E.g. PP or pp Heterozygous individuls hve two different lleles for chrcter. E.g. Pp lleles re lterntive versions of genes found t the specific locus (position) of tht gene. Orgnisms inherit two lleles one from ech prent iology Olympid Preprtion Progrm 17 Genotype nd phenotype The dominnt llele is expressed fully, whilst the recessive llele hs no noticele effect. E.g. llele P overshdows the effect of llele p. Only recessive homozygotes hve the recessive phenotype. Genotype orgnism s genetic mkeup, e.g. Pp. Phenotype orgnism s trits, e.g. purple iology Olympid Preprtion Progrm 18 The lw of segregtion The lw of segregtion sttes tht the two lleles for ech chrcter segregte during gmete production. True-reeding prentl gmetes re P from purple prent nd p from white prent. F 1 gmetes re either P or p. F 2 genertion: 25% PP, 50% Pp, 25% pp. Punnet squre iology Olympid Preprtion Progrm 19 3
4 *Exmple Independent segregtion of lleles P: Gmetes: F 1 : Gmetes: F 2 : iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 21 The testcross The lw of independent ssortment Useful for determining genotype of individuls with known phenotype. Dihyrid cross. testcross involves the reeding of recessive homozygote (white, pp) with n orgnism of dominnt phenotype (purple) ut unknown genotype (PP or Pp). Two pirs of lleles segregte independently of ech other iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 23 P: Gmetes: F 1 : GG G *Exmple Gg gg g Gmetes: G g G g F 2 : GG Gg gg gg GG Gg gg Gg G g G g 2004 iology Olympid Preprtion Progrm 24 Mendelin genetics nd proility If gene hs 2 lleles, one gmete hs 50% chnce of hving prticulr llele for tht gene. Chnce of PP is ½ ½ = ¼ Chnce of Pp is ½ ½ = ¼ Chnce of pp is ½ ½ = ¼ Therefore chnce of heterozygote is ¼ + ¼ = ½ Chnce of pp is ½ ½ = ¼ 2004 iology Olympid Preprtion Progrm 25 4
5 Exmple P: PpYyRr Ppyyrr F 1 : Chnce of getting t lest two recessive trits: ppyyrr ppyyrr Ppyyrr PPyyrr ppyyrr Pr(pp) nd Pr(yy) nd Pr(Rr) = ½ ½ ½ ½ = 1/16 ¼ ½ ½ = 1/16 ½ ½ ½ = 2/16 ¼ ½ ½ = 1/16 ¼ ½ ½ = 1/16 Pp mens Pp or pp hence ½ ½ + ½ ½ = 2/4 = ½ Mendelin genetics, in summry Mendel performed his experiments so tht he could determine ptterns of inheritnce y knowing the prentge of new seeds. Chrcters re heritle fetures nd trits re vritions of chrcters. True-reeding individuls re homozygous for the prticulr gene under study. The P genertion is the prentl genertion, nd F 1 nd F 2 re the first nd second filil genertions respectively. lleles re different vritions of gene found t prticulr locus on chromosome. Dominnt lleles re expressed fully while recessive lleles hve no noticele effect on ppernce. 6/ iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 27 Mendelin genetics, in summry Homozygous individuls (homozygotes) hve two of the sme llele for gene. Heterozygous individuls (heterozygotes) hve two different lleles for gene. n orgnism s genetic mkeup is its genotype. Its phenotype is n expression of its genotype. Recessive homozygotes express the recessive phenotype, while heterozygotes nd dominnt homozygotes express the dominnt phenotype. The lw of segregtion sttes tht two lleles for ech chrcter segregte during gmete formtion. Mendelin genetics, in summry The testcross is useful tool where n unknown genotype dominnt phenotype individul is crossed with n individul with recessive phenotype. The lw of independent ssortment sttes tht two pirs of lleles segregte independently of ech other. Results of Mendelin crosses cn e quickly nd esily clculted using the lws of proility iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 29 NON-MENDELIN GENETICS Incomplete dominnce & codominnce Mendel s lws ssume complete dominnce i.e. one llele is dominnt, nother recessive. Incomplete dominnce heterozygotes hve phenotype intermedite etween homozygous phenotypes. E.g. snpdrgon colour (left). Codominnce oth lleles ffect phenotype. E.g. MN lood groups iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 31 5
6 Multiple lleles & pleiotropy Epistsis & polygenicity Multiple lleles more thn 2 lleles for gene. E.g. O lood types. Importnt in determining lood comptiility. Pleiotropy one llele hs mny phenotypic effects. E.g. sickle cell disese iology Olympid Preprtion Progrm 32 Epistsis one gene ffects the phenotypic expression of nother. E.g. cot colour in mice. Polygenic inheritnce two or more genes ffecting single phenotype. E.g. skin colour iology Olympid Preprtion Progrm 33 Phenotype nd the environment Phenotype depends on environment s well s genotype. Multifctoril chrcters re ffected y mny fctors. E.g. hydrnge colour. I II Pedigrees Ff Ff Ff ff FF/ Ff ff ff Ff Ff ff Flowers turn different colour in different soil phs. Red in lkline, lue in cid. III Nomenclture: ff Norml mle FF/ Ff Norml femle P = G + E. Crrier mle. ffected mle Crrier femle ffected femle 2004 iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 35 Chromosomes nd Mendel s lws lternte rrngements of homologous chromosomes on the metphse plte during metphse I ccount for the lw of independent ssortment. The seprtion of homologues nd sister chromtids in nphse I nd II, respectively, ccount for the lw of segregtion iology Olympid Preprtion Progrm 36 Sex determintion nd chromosomes In most nimls, there is chromosoml sis ehind sex determintion. XY: mmmls. Sperm is either X or Y. XX femle, XY mle. X0: some insects. Sperm either crries or doesn t crry the X (sex) chromosome. XX femle, X0 mle. ZW: irds, fish, some insects. Ovum is either Z or W. ZW femle, ZZ mle. Hplo-diploid: ees nd nts. Femles diploid, mles hploid iology Olympid Preprtion Progrm 37 6
7 Sex linkge Sex-linked genes re crried on sex chromosomes (either X or Y). E.g. eye colour in Drosophil, the fruit fly studied y Morgn. Wild type lleles (norml phenotype) of chrcter written with superscript +. Mutnt lleles written without it. F 2 genertion showed typicl 3:1 rtio, ut only mles were white eyed it ws linked to sex iology Olympid Preprtion Progrm 38 Linked genes distnce etween two genes, likelihood of eing inherited together these re linked genes. E.g. Fruit fly ody colour nd wing type (left). Independent ssortment does not occur ll the time with linked genes. Recominnt phenotypes hve new comintions of trits. Prentl phenotypes hve the prentl comintions iology Olympid Preprtion Progrm 39 Recomintion Recominnts produced y crossing over during meiosis I. Recomintion frequency is mesure of how closely linked two genes re iology Olympid Preprtion Progrm 40 Linkge mps Recomintion frequency is representtive of the reltive distnce etween two genes on the sme chromosome. We cn uild linkge mps out of recomintion frequency dt to determine the reltive positions of genes on chromosomes. Good for Drosophil s they reed quickly. Not so good for humns. So how do we do it? 2004 iology Olympid Preprtion Progrm 41 Non-Mendelin genetics, in summry Incomplete dominnce involves heterozygotes hving phenotype intermedite etween those of the two types of homozygotes. In codominnce, heterozygote exhiits phenotypes for oth its lleles. Mny genes exist in multiple lleles in popultion. Pleiotropy is the ility of single gene to ffect multiple phenotypic trits. In epistsis, one gene ffects the expression of nother gene. Chrcters tht re quntittive, vrying continuously, indicte polygenic inheritnce, n dditive effect of two or more genes on single phenotypic chrcter. Non-Mendelin genetics, in summry Environment plys role in determining n orgnism s phenotype. Fmily pedigrees cn e used to deduce the possile genotypes of individuls nd mke predictions out future offspring. Mendelin inheritnce hs its physicl sis in the ehviour of chromosomes during meiosis nd fertilistion. Sex is n inherited phenotypic chrcter usully determined y the presence or sence of specil chromosome. Mmmls use the XY system of sex determintion. Sex-linked genes hve unique ptterns of inheritnce. Linked genes re situted close to ech other on the chromosome nd re likely to e inherited together iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 43 7
8 Non-Mendelin genetics, in summry The recomintion frequency is mesure of how close two genes re on the sme chromosome. Recominnt phenotypes re due to crossing over during meiosis. Linkge mps cn e constructed from recomintion frequencies. Eukryotic genetics cteril nd virl genetics Next time When? 2004 iology Olympid Preprtion Progrm iology Olympid Preprtion Progrm 45 8
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