* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Ch 4 Extensions of Mendelian Genetics
Epigenetics of neurodegenerative diseases wikipedia , lookup
X-inactivation wikipedia , lookup
Minimal genome wikipedia , lookup
Saethre–Chotzen syndrome wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Genetic engineering wikipedia , lookup
Frameshift mutation wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Genetic drift wikipedia , lookup
Gene therapy wikipedia , lookup
Gene desert wikipedia , lookup
Neuronal ceroid lipofuscinosis wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
History of genetic engineering wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Population genetics wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Gene nomenclature wikipedia , lookup
Genomic imprinting wikipedia , lookup
Oncogenomics wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Genome (book) wikipedia , lookup
Mitochondrial DNA wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Gene expression programming wikipedia , lookup
Genome evolution wikipedia , lookup
Helitron (biology) wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Gene expression profiling wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Point mutation wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Designer baby wikipedia , lookup
1/21/2016 Ch 4 Extensions of Mendelian Genetics Exceptions to Mendelian Ratios 1 Alleles can alter phenotypes • Wild-type allele: allele most frequently seen in the population • Loss-of-function allele: mutation alters gene in such a way that the protein is less-functional or non-functional; • The degree to which the function is lost can vary. If the function is entirely lost, the mutation is called a null mutation. Loss of function mutations are typically recessive. When a heterozygote consists of the wild-type allele and the loss-of-function allele, the level of expression of the wild type allele is often sufficient to produce the wild type phenotype. • Null allele: above, but complete loss of function 2 1 1/21/2016 Alleles can alter phenotypes • And… • Gain-of-function allele: mutation alters gene in such a way that the protein’s function is enhanced • Neutral mutations: mutation that does not alter protein function • Remember the “Central Dogma of Molecular Biology” is that DNA→mRNA→ribosome/tRNA→polypeptide 3 Nomenclature and symbols • In Drosophila we can use this system for distinguishing traits. In this example, ebony is the recessive body color. • e+ / e+ OR + / + - gray homozygote (WildType) • e+ / e OR + / e - gray heterozygote (WildType) • e / e OR e / e - ebony homozygote (mutant) • We will also use other systems for distinguishing traits. 4 2 1/21/2016 Incomplete Dominance Crosses between true-breeding strains can produce hybrids with phenotypes different from both parents. Incomplete dominance F1 hybrids that differ from both parents express an intermediate phenotype. Neither allele is dominant or recessive to the other. Phenotypic ratios are same as genotypic ratios Codominance F1 hybrids express phenotype of both parents equally. Phenotypic ratios are same as genotypic ratios.5 Snapdragons- Incomplete Dominance Figure 4-1 1:2:1 Copyright © 2010 Pearson Education, Inc. 3 1/21/2016 Dominance Relationships 7 Co-dominance Domesticated 10,000 years 1:2:1 in F2 8 4 1/21/2016 The terminus of H Antigen defines blood type Co-dominance 9 Codominance 10 5 1/21/2016 A Gene May Have More Than 2 Alleles 11 Bombay Phenotype 12 6 1/21/2016 Individuals with genotype hh do not make the H glycoprotein (the molecular base for A and B) Consequently it appears (types) as just oo) 13 The Bombay Phenotype Copyright © 2010 Pearson Education, Inc. 7 1/21/2016 Example: many alleles of “white” eyes Copyright © 2010 Pearson Education, Inc. Recognized alleles for Brown Hair 16 8 1/21/2016 Agouti (A, dominant) gene has varied effects in mammal coat color Named for cental/south american mammal; They are related to guinea pigs 17 Mutations are the source of new alleles Dominant A, and any other allele “Dominance Series: A>at>a” 18 9 1/21/2016 The Agouti Yellow allele (AY) is dominant to A but lethal when Homozygous (lethality is recessive) i.e. AY AY do not exist 19 Figure 4-3 Copyright © 2010 Pearson Education, Inc. 10 1/21/2016 AY A AY AY die A AY A A AY A AY A AA 2:1 phenotype ratio 21 Heterogeneous traits have multiple genes underlying their expression • Gene interaction • It is not always possible to determine which of many genes are mutated in a person with a heterogeneous mutant phenotype. Example – deafness in humans may be caused by a mutant allele at one of more than 50 different genes. 22 11 1/21/2016 Epistasis – One gene’s alleles mask the effects of another gene’s alleles Epistasis: A gene interaction where the allele of one gene masks/hides the effects of alleles of another gene. -The gene doing the masking is epistatic to the gene being masked (hypostatic gene) -Bombay phenotype is an example of epistasis (hh is epistatic to which codes for A and B antigens) 23 Figure 4-5 Not even close to 9:3:3:1 of a dihybrid cross Copyright © 2010 Pearson Education, Inc. 12 1/21/2016 Labrador retriever example – recessive epistasis Coat color can be black, chocolate brown, or golden yellow B allele is dominant and determines black. b allele is recessive and determines brown if homozygous. E allele at second gene has no affect on coat color. e allele is recessive and if homozygous hides effects of black or brown alleles. -BBEE (black pure breeding) X bbee (golden pure breeding) produce BbEe black F1 offspring. -BbEe X BbEe produce 9 black (B_E_) for every 3 brown (bbE_), and 4 gold (__ee). 9:3:4 is a telltale ratio of recessive epistasis. 25 Lab Retrievers and Epistasis 13 1/21/2016 Lab Retrievers and Epistasis Black “B” is dominate to Chocolate “b” A second gene E will mask the Black/Choc Gene if homozygous recessive “ee” producing yellow lab Lab Retrievers and Epistasis Black “B” is dominate to Chocolate “b” A second gene E will mask the Black/Choc Gene if homozygous recessive “ee” producing yellow lab bbEE or bbEe BBEE BbEE BBEe BbEe BBee Bbee bbee 14 1/21/2016 9:3:4 recessive epistasis 30 15 1/21/2016 Summer Squash- dominant epistasis Copyright © 2010 Pearson Education, Inc. Any “B” white 12:3:1 Dominant Epistasis 32 16 1/21/2016 Complementary gene action Two different genes work together to produce a phenotype. 9:7 ratio is a phenotypic signature of complementary gene interaction where dominant alleles of two genes act together to produce a trait while other three genotypic classes do not. 33 9:7 34 17 1/21/2016 35 36 18 1/21/2016 Complementation - different homozygous recessive mutations that produce the same mutant phenotype (e.g., wingless) produce wildtype (non-mutant) when crossed. Complementation will not occur if the mutations are in the same gene. 37 Complementation Analysis (Two genes or one gene) Two homozygous recessive flies Two homozygous recessive flies “Linked genes! 1x1 Punnett” Effectively Homozygous mutant Normal wild type progeny if Cross was with two genes; Progeny have wildtype alleles for both genes Copyright © 2010 Pearson Education, Inc. 19 1/21/2016 The left Side of Previous Slide Each can make only one gamete: left individual + means wildtype m a+ x right individual +mb ma+mb+ “heterozygotes” +ma or +mb will not produce wingless mutant 39 The Right Side of Previous Slide Each can make only one gamete: + means wildtype mamb++ left individual right individual ma+ x mb+ Effectively Homozygous mutant 40 20 1/21/2016 One gene may contribute to several visible characteristics Pleiotropy – single gene determines more than one distinct and seemingly unrelated characteristic Some alleles may cause lethality. Type of pleiotropy where alleles produce a visible phenotype and affect viability Alleles that affect viability often produce deviations from a 1:2:1 genoptypic and 3:1 phenotypic ratio predicted by Mendel’s Laws. 41 a. Inbred agouti X yellow yields 1:1 agouti:yellow Yellow must be AYA and AY is dominant to A b. Yellow x yellow mice do not breed true. AY is a recessive lethal. AYAY die in utero and do not show up as progeny 42 21 1/21/2016 X-linked Genes Figure 4-10 Copyright © 2010 Pearson Education, Inc. w+ is wildtype or red 44 22 1/21/2016 Table 4-2 Copyright © 2010 Pearson Education, Inc. X and Y linked traits in humans are identified by pedigree analysis. • X-linked traits exhibit five characteristics seen in pedigrees. 1. 2. 3. 4. 5. Trait appears in more males than females. Mutation and trait never pass from father to son. Affected male does pass X-linked mutation to all daughters, who are heterozygous carriers. Trait often skips a generation. Trait only appears in successive generations if sister of an affected male is a carrier. If 46 so, one half of her sons will show trait. 23 1/21/2016 Figure 4-12 Copyright © 2010 Pearson Education, Inc. Pedigree of colorblindness (X-linked)assign phenotypes and genotypes 48 24 1/21/2016 49 50 25 1/21/2016 51 Extranuclear Inheritance •How genetic transmission revealed and explained non-Mendelian patterns of inheritance •Mitochondria and chloroplasts •Examples of mutations in mitochondrial DNA that affect human health •Maternal effect 52 26 1/21/2016 Mitochondrial and chloroplasts are organelles of energy conversion that carry their own DNA •Chloroplasts – capture solar energy and store it in carbohydrates •Mitochondria – release energy from nutrients and convert it to ATP 53 Origin and evolution of organelle genomes: molecular evidence • Endosymbiotic theory – Mitochondria and chloroplasts originated more than a billion years ago. – Ancient precursors of eukaryotic cells engulfed bacteria and established symbiotic relationship. – Molecular evidence • Both chloroplasts and mitochondria have own DNA • mtDNA and cpDNA are not organized into nucleosomes by histones, similar to bacteria. • Mitochondrial genomes use N-formyl methionine and tRNAfmet in translation…just like bacteria! 27 1/21/2016 Four-o’clocks- Example of maternal inheritance Copyright © 2010 Pearson Education, Inc. Yeast! – Mitochondrial Inheritance Copyright © 2010 Pearson Education, Inc. 28 1/21/2016 • Maternal inheritance of Xenopus mtDNA Purified mtDNA from two species Hybridization only to probes from same species F1 hybrids retain only mtDNA from mother. • • • mtDNA – at the gene level • • 16.5 kb in length Carries 37 genes • • • • 13 proteins required for cellular respiration 22 tRNA genes 2 genes for large and small rRNAs Compact gene arrangement • • No introns Genes abut or slightly overlap. 29 1/21/2016 Criteria for a mitochondrial inherited disorder • Maternal inheritance pattern- not Mendel • Disorder is due to deficiency in bioenergetics of the mitochondria • Genetic mutation identified in at least one mitochondrial gene 16-59 Cells can contain one type or a mixture of organelle genomes. • Heteroplasmic – cells contain a mixture of organelle genomes – Mitotic products may contain one type, a mixture of types, or the second type. • Homoplasmic – cells contain one type of organelle DNA – Mitotic products contain same type, except for rare mutation. 16-60 30 1/21/2016 LHON- Leber’s hereditary optic neuropathy Mitotic segregation produces an uneven distribution of organelle genes in heteroplasmic cells. • Women with heteroplasmic LHON mutation – Some ova may carry few mitochondria with LHON mutation and large number of wild-type. – Other ova may carry mainly mitochondrial with LHON mutation and few wild-type. – Consequence of heteroplasmy after fertilization • Some cells produce tissues with normal ATP production and others with low production. • If low production cells are in optic nerve, LHON 16-62 results. 31 1/21/2016 • Individuals with certain rare diseases of the nervous system are heteroplasmic. • • MERRF Uncontrolled jerking, muscle weakness, deafness, heart problems, kidney problems, progressive dementia MERRF 32 1/21/2016 Mitochondrial inheritance in identical twins • Mitochondrial genomes not same in twins but nuclear genomes are identical – Symptoms of neurodegenerative diseases or other mutations may manifest in one twin, but not other. – In a heteroplasmic mother, chance of phenotype of offspring depends on both partitioning of mutant mtDNA after fertilization, and tissue that receives mutation during development. 16-65 Maternal effect (aka maternal influence) • Nuclear genes of female gamete are transcribed, and the gene products accumulate in egg cytoplasm. • After fertilization, the gene products are partitioned to newly formed cells and can influence gene function during early development. 16-66 33 1/21/2016 Maternal effect- meal moth example Copyright © 2010 Pearson Education, Inc. 34