* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Gene mutation
Gene desert wikipedia , lookup
Gene expression profiling wikipedia , lookup
DNA damage theory of aging wikipedia , lookup
Genetic code wikipedia , lookup
DNA vaccination wikipedia , lookup
Deoxyribozyme wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Gene therapy wikipedia , lookup
Cancer epigenetics wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Zinc finger nuclease wikipedia , lookup
Messenger RNA wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Population genetics wikipedia , lookup
Genetic engineering wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Gene expression programming wikipedia , lookup
Epitranscriptome wikipedia , lookup
Gene nomenclature wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Non-coding DNA wikipedia , lookup
Oncogenomics wikipedia , lookup
Genome (book) wikipedia , lookup
History of genetic engineering wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Neuronal ceroid lipofuscinosis wikipedia , lookup
Genome evolution wikipedia , lookup
Genome editing wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Saethre–Chotzen syndrome wikipedia , lookup
Primary transcript wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Designer baby wikipedia , lookup
Helitron (biology) wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Microevolution wikipedia , lookup
Mutations - What is meant by ‘mutation’? - When/how do they happen? - What sort of impact might they have? 8.7 in text - Mutations Some definitions gene: a segment of nucleic acid that controls a specific trait. Most familiarly structural genes (coding for a protein), but also including rRNA, tRNA, and regulator sequences. allele: one of several possible versions of a gene, found at the same chromosomal site (gene locus) as other alleles of the same gene. chromosome: in eukaryotes a complete linear (double) strand of DNA with accompanying proteins. In prokaryotes the chromosome is circular, and there is only one. genome: an organism’s entire complement of genetic material… May be applied to mean only one set of chromosomes (diploids would be said to have 2 genomes in somatic cells). May or may not be used to include mitochondrial/chloroplast DNA. Gene mutation (point mutation) : base pair substitution “Wild Type” DNA ...GCTATGACCATGATTACGGATTCACTG... ...CGATACTGGTACTAATGCCTAAGTGAC... mRNA ↓ transcription ...GCU AUG ACC AUG AUU ACG GAU UCA CUG Protein ↓ translation (without anticodons) Met-Thr - Met - Ile- Thr - Asp-Ser- Leu... Missense mutation DNA base swapped ↓ ...GCTATGACCATGATTAGGGATTCACTG... ...CGATACTGGTACTAATCCCTAAGTGAC... mRNA ↓ transcription ...GCU AUG ACC AUG AUU AGG GAU UCA CUG... Protein ↓ translation Met-Thr - Met - Ile -Arg -Asp-Ser-Leu... In sickle-cell anemia, a point mutation, leading to a one amino acid change, makes a significant change in the resulting hemoglobin. Hb β → ATG GTG CAC CTG ACT CCT GAG GAG AAG TCT GCC GTT ACT.. Hb s → ATG GTG CAC CTG ACT CCT GTG GAG AAG TCT GCC GTT ACT.. MVHLTPEEKSAVT.. (E is the single letter abbreviation for glutamic acid) MVHLTPVEKSAVT.. (V is the single letter abbreviation for valine) This is the coding sequence for the entire normal β protein of hemoglobin (there are two α and two β proteins per hemoglobin). Here is the substituted nucleotide. ↓ ATGGTGCACCTGACTCCTGAGGAGAAGTCTGCGGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAG TTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGG GGATCTGTCCACTCCTGATGCAGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGT GCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACT GTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCA TCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAAT GCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCC CTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAA CATTTATTTTCATTGC Unaffected hemoglobin molecule site of hydrophilic glutamic acids that get swapped ↓ ←β chains ← heme group ←α chains Substituting hydrophobic valine for the glutamic acids at that one locus causes the hemoglobins to clump together, causing a series of symptoms… http://genomics.energy.gov/ www.bio.davidson.edu/.../2005/Eppolito/intro.htm Should fetuses be screened? Sickle-cell trait is the inheritance of only one copy of the gene: This is generally asymptomatic, and confers resistance to malaria. so, S-C anemia is a classic illustration of natural selection. There are similar hemoglobin variations in other sub-tropical areas of the globe. Gene mutation: substitution (cont.) “Wild Type” DNA ...GCTATGACCATGATTACGGATTCACTG... ...CGATACTGGTACTAATGCCTAAGTGAC... mRNA ↓ transcription ...GCU AUG ACC AUG AUU ACG GAU UCA CUG Protein ↓ translation (without anticodons) Met-Thr- Met- Ile - Thr - Asp- Ser- Leu... Nonsense Mutation DNA base swapped ↓ ...GCTATGACCATGATTACGGATTGACTG... ...CGATACTGGTACTAATGCCTAACTGAC... mRNA ↓ transcription ...GCU AUG ACC AUG AUU ACG GAU UGA CUG... Protein ↓ translation Met -Thr- Met- Ile - Thr- Asp (UGA = stop) Gene mutations: insertion/deletion “Wild Type” DNA ...GCTATGACCATGATTACGGATTCACTG... ...CGATACTGGTACTAATGCCTAAGTGAC... mRNA ↓ transcription ...GCU AUG ACC AUG AUU ACG GAU UCA CUG Protein ↓ translation (without anticodons) Met-Thr- Met- Ile - Thr - Asp- Ser- Leu... Frameshift Mutation DNA ↓ added base ...GCTATGACCCATGATTACGGATTCACTG... ...CGATACTGGGTACTAATGCCTAAGTGAC... mRNA ↓ transcription ...GCU AUG ACC CAU GAU UAC GGA UUC ACU G... Protein ↓ translation Met -Thr- His -Asp-Tyr-Gly- Phe-Thr- Example of a problem caused by a frame shift mutation: “People with thalassemia make less hemoglobin [because the mRNA degrades faster] and have fewer circulating red blood cells than normal, which results in mild to severe anemia. .... “Cases of dominantly inherited α- and β-thalassemias have been reported, the first of which was in an Irish family with two deletions of 4 and 11 bp in exon 3 interrupted by an insertion of 5 bp in the β -globin gene. .... “Having a single gene for thalassemia may protect against malaria and thus be an advantage. People diagnosed with heterozygous β-thalassemia have some protection against coronary heart disease.” Wikipedia http://www.haematologica.org/content/96/6/905 Chromosomal mutations: Usually occur when chiasmata form in prophase I. deletion, duplication, inversion, translocation (recap from meiosis section) Chromosomal mutations: nondisjunction -Occurs when chromosomes fail to properly separate in anaphase I or anaphase II of meiosis - Results in aneuploidy (wrong number of chromosomes), Most aneuploidy in humans is non-viable. Autosomal trisomy: Trisomy 21 (Down syndrome) Trisomy 18 (Edwards syndrome) Trisomy 13 (Patau syndrome) Trisomy 12 (Chronic Lymphocytic Leukemia) Trisomy 8 (Warkany syndrome 2) Trisomy 9 X/Y-linked aneuploidy is more likely to be viable. Mutations are a source of genetic variability within a population. They can occur any time DNA is replicated and cells divide (some occur between replications). But the ones that have the biggest ramifications are ones that occur in gamete formation (meiosis) because that alteration will occur in every cell of any resulting offspring. What is a gene mutation? Describe an example of a specific type. What is a chromosomal mutation? Describe an example of a specific type. What is the role of complementary base pairing in replication, in transcription, and in translation? And how might this go wrong? Should we be worried about all mutations? (Hm…. That sounds like a “No”…) Defend your answer. gene structural gene allele gene locus chromosome genome gene mutation point mutation base pair substitution missense mutation nonsense mutation insertion/deletion frameshift mutation chromosomal mutation chromosomal deletion chromosomal duplication chromosomal inversion chromosomal translocation nondisjunction aneuploidy autosomal trisomy