DOCSLIB.ORG

Supplementary Table 3

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Table 3 Supplementary Table 3: Summary of HPRT Mutations from Normal Childrena Subject Gender Age Mutant Class of Mutation Mutant cDNA Frequency (10-6) Number Children 6-11 yrs. BF053B1 M 6.4 5.4 Transition (1) M4 c.3G>A BF064B1 M 8.1 4.1 Transition (1) M10 c.568G>A BF018B1 M 8.7 0.5 Transition (1) M1 Exclusion: 8 BF048B1 M 8.9 2.2 Transition (1) M4 c.209G>A BF012B1 F 9.0 9.0 Transition (1) M13 c.212G>A BF012B1 F 9.0 9.0 Transition (1) M2 c.113C>T BF058B1 F 10.9 0.8 Transition (1) M1 Exclusion: 2,3 BF064B1 M 8.1 4.1 CpG Transition (3) M1 c.151C>T BF064B1 M 8.1 4.1 CpG Transition (3) M12 c.151C>T BF023B1 F 7.5 1.4 Transversion (4) M3 c.434C>A BF064B1 M 8.1 4.1 Transversion (4) M4 c.575C>A BF001B1 M 10.7 2.0 Transversion (4) M3 c.486C>A BF064B1 M 8.1 4.1 Transversion (5) M19 c.569G>C BF105B1 M 6.8 2.0 Transversion (6) M2 c.466A>T BF105B1 M 6.8 2.0 Transversion (7) M4 c.484A>C BF015B1 F 7.7 8.7 Transversion (7) M1 c.389T>G BF064B1 M 8.1 4.1 Transversion (7) M15 c.284T>G BF064B1 M 8.1 4.1 Exon Deletion (8) M16 BF064B1 M 8.1 4.1 Exon Deletion (8) M18 BF064B1 M 8.1 4.1 Exon Deletion (8) M20 BF064B1 M 8.1 4.1 Exon Deletion (8) M5 BF109B1 M 10.5 21.0 Exon Deletion (8) M3 BF001B1 M 10.7 2.0 Exon Deletion (8) M4 BF015B1 F 7.7 8.7 Microdeletion (9) M3 Exclusion: Range: 1-14 BF015B1 F 7.7 8.7 Microdeletion (9) M4 Exclusion: Range: 1-6 BF001B1 M 10.7 2.0 Microdeletion (9) M1 c.549delT BF023B1 F 7.5 1.4 Duplication (10) M2 c.304dupC BF064B1 M 8.1 4.1 Insertion (11) M17 c.499_500insA BF124B1 F 10.0 8.0 Insertion (11) M1 c.502_503insG BF001B1 M 10.7 2.0 Insertion (11) M2 c.589_590insT BF012B1 F 9.0 9.0 Deletion/Insertion (12) M1 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M10 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M3 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M4 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M6 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M7 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M8 c.568_569delGGinsAA BF012B1 F 9.0 9.0 Deletion/Insertion (12) M9 c.568_569delGGinsAA BF101B1 M 9.1 3.3 Incompletely Characterized (16) M3 Exclusion: 2,3,4,5,6,7,8,9 BF124B1 F 10.0 8.0 Incompletely Characterized (16) M2 Exclusion: 8 Children 12-16 yrs. BF007B1 M 12.5 4.0 Transition (1) M7 c.212G>A BF019B1 F 13.2 4.0 Transition (1) M10 Inclusion: 1+1 to 1+49 BF102B1 F 13.5 3.4 Transition (1) M2 BF113B1 F 13.5 6.5 Transition (1) M1 c.568G>A BF113B1 F 13.5 6.5 Transition (1) M2 c.580G>A BF005B1 F 13.9 1.2 Transition (1) M4 c.617G>A BF021B1 F 15.2 4.3 CpG Transition (3) M10 c.508C>T BF007B1 M 12.5 4.0 Transversion (4) M6 c.135G>T BF102B1 F 13.5 3.4 Transversion (4) M4 c.617G>T BF021B1 F 15.2 4.3 Transversion (4) M3 Exclusion: 7 BF021B1 F 15.2 4.3 Transversion (4) M5 Exclusion: 7 BF007B1 M 12.5 4.0 Transversion (5) M1 c.648C>G BF007B1 M 12.5 4.0 Transversion (5) M2 Exclusion: 7 BF113B1 F 13.5 6.5 Transversion (5) M5 c.190G>C BF104B1 M 15.7 4.2 Transversion (5) M1 Exclusion: 7 BF004B1 M 13.2 7.0 Transversion (6) M2 Exclusion: Range: 610-626 BF019B1 F 13.2 4.0 Transversion (6) M5 Exclusion: 8 BF005B1 F 13.9 1.2 Transversion (7) M2 c.136A>C BF007B1 M 12.5 4.0 Exon Deletion (8) M10 BF007B1 M 12.5 4.0 Exon Deletion (8) M5 BF007B1 M 12.5 4.0 Exon Deletion (8) M9 BF004B1 M 13.2 7.0 Exon Deletion (8) M3 BF104B1 M 15.7 4.2 Exon Deletion (8) M5 BF006B1 F 12.5 1.9 Microdeletion (9) M3 c.165_169delGGAGA BF102B1 F 13.5 3.4 Microdeletion (9) M2 Exclusion: 2,3,4 BF006B1 F 12.5 1.9 Loss (10) M5 c.402losA BF113B1 F 13.5 6.5 Loss (10) M4 c.484losA BF006B1 F 12.5 1.9 Incompletely Characterized (16) M6 Exclusion: 8 BF006B1 F 12.5 1.9 Incompletely Characterized (16) M7 Exclusion: 2,3 BF007B1 M 12.5 4.0 Incompletely Characterized (16) M8 Exclusion: 8 Summary of HPRT Mutations from Adultsb Number ID SUBJECT SEX AGE MF Smoking Status MUTANT 311 2000H Male 23 20.0 Non-Smoke 2812F12 303 900H Male 29 21.0 Non-Smoke 91B8 304 900H Male 29 21.0 Non-Smoke 92F1 306 900H Male 29 21.0 Non-Smoke 91G10 79 sf21.1 Female 25 7.0 Smoker 35D8 118 sm25.1 Male 22 7.0 Smoker 49A1 69 nm28.1 Male 23 4.0 Non-Smoke 24 E7 94 sm30.1 Male 24 7.0 Smoker 66D7 93 nm19.1 Male 31 5.0 Non-Smoke 34F5 105 sm5.1 Male 38 2.0 Smoker 14B6 248 sf32 Female 29 5.0 Smoker 37 E11 244 nf45 Female 31 10.0 Non-Smoke 56B5 241 sf33 Female 31 10.0 Smoker 39B10 245 sf34 Female 31 10.0 Smoker 75C9 247 nf3 Female 45 4.0 Non-Smoke 20B2 243 nf43 Female 46 16.0 Non-Smoke 49H1 207 nm37 Male 20 4.0 Non-Smoke 77A9 219 nm31 Male 21 5.0 Non-Smoke 26H7 229 nm29 Male 23 5.0 Non-Smoke 58F9 222 sm2 Male 25 14.0 Smoker 14C11 212 nm46 Male 26 19.0 Non-Smoke 39 D6 238 nm17 Male 26 8.0 Non-Smoke 24A10 216 nm30 Male 27 5.0 Non-Smoke 17G1 231 nm35 Male 27 3.0 Non-Smoke 55B7 226 nm11 Male 29 9.0 Non-Smoke 59BD7 214 sm45 Male 31 7.0 Smoker 28G2 251 sm64 Male 32 12.0 Smoker 66F6 215 sm77 Male 37 5.0 Smoker 48F2 223 sm82 Male 37 13.0 Smoker 15A2 208 sm79 Male 38 8.0 Smoker 69H10 218 sm100 Male 39 12.0 Smoker 86F4 233 nm38 Male 40 4.0 Non-Smoke 27C1 235 nm38 Male 40 4.0 Non-Smoke 27 E2 213 sm41 Male 40 15.0 Smoker 66 E5 224 sm91 Male 41 12.0 Smoker 74C12 209 sm108 Male 42 11.0 Smoker 75 E7 242 sm92 Male 43 14.0 Smoker 59G10 230 sm38 Male 45 18.0 Smoker 18B3 221 sm113 Male 46 6.0 Smoker 38H1 236 sm75 Male 48 17.0 Smoker 88H12 225 sm90 Male 50 19.0 Smoker 79F3 314 325 Male 50 13.0 Smoker 325-3-21 319 325 Male 50 13.0 Smoker 325-2-20 320 325 Male 50 13.0 Smoker 325-2-21 334 325 Male 50 13.0 Smoker 325-2-28 338 325 Male 50 13.0 Smoker 325-3-10 341 325 Male 50 13.0 Smoker 325-3-33 6 17S Female 37 3.0 Smoker 17-2-29 297 42H Male 22 Non-Smoke 42 D2 286 89F42 Male 24 19.0 Non-Smoke 942/4 289 20A Male 25 Non-Smoke 20C11 296 53H Male 55 Non-Smoke 53A11 739 1M0 Female 66 27.0 Non-Smoke 1M0-4 752 14M0 Female 70 33.0 Smoker 14M0-16 726 4M0 Male 55 78.0 Smoker 4M0-8 786 4M0 Male 55 78.0 Smoker 4M0-2 738 7M0 Male 62 34.0 Non-Smoke 7M0-4 777 7M0 Male 62 34.0 Non-Smoke 7M0-14 780 7M0 Male 62 34.0 Non-Smoke 7M0-13 773 3M0 Male 63 132.0 Smoker 3M0-8 760 9M0 Male 77 28.0 Smoker 9M0-9 778 9M0 Male 77 28.0 Smoker 9M0-7 753 18M0 Male 82 45.0 Non-Smoke 18M0-1 59 16EO Female 75 18.0 Smoker 16E0-8 39 22EO Male 66 32.0 Smoker 22E0-5 28 8EO Male 68 73.0 Smoker 8E0-3 14 9EO Male 69 9.0 Smoker 9E0-1 32 3EO Male 77 25.0 Smoker 3E0-21 13 24EO Male 78 26.0 Non-Smoke 24E0-6 51 1EO Male 80 18.0 Smoker 1E0-5 52 1EO Male 80 18.0 Smoker 1E0-3 694 V128 Male 31 6.0 Non-Smoke V128 698 V127 Male 31 11.0 Non-Smoke V127 711 V127 Male 31 11.0 Non-Smoke V127 713 V127 Male 31 11.0 Non-Smoke V127 672 V124 Male 39 5.0 Non-Smoke V124 697 K28 Male 44 15.0 Non-Smoke K28 718 K33 Male 52 20.0 Non-Smoke K33 695 K25 Male 54 11.0 Non-Smoke K25 645 K27 Male 23 6.0 Non-Smoke K27 547 K34 Male 30 6.0 Non-Smoke K34 625 K34 Male 30 6.0 Non-Smoke K34 636 K32 Male 30 1.0 Non-Smoke K32 571 V127 Male 31 11.0 Non-Smoke V127 612 K37 Male 32 5.0 Non-Smoke K37 642 K26 Male 33 5.0 Non-Smoke K26 559 V123 Male 35 6.0 Non-Smoke V123 551 K29 Male 36 6.0 Non-Smoke K29 584 K29 Male 36 6.0 Non-Smoke K29 602 V148 Male 37 9.0 Non-Smoke V148 569 V133 Male 38 14.0 Non-Smoke V133 601 V150 Male 38 3.0 Non-Smoke V150 638 V150 Male 38 3.0 Non-Smoke V150 640 V150 Male 38 3.0 Non-Smoke V150 610 K28 Male 44 15.0 Non-Smoke K28 588 K33 Male 52 20.0 Non-Smoke K33 624 V141 Male 52 16.0 Non-Smoke V141 650 V132 Male 52 9.0 Non-Smoke V132 590 K25 Male 54 11.0 Non-Smoke K25 575 V143 Male 61 8.0 Non-Smoke V143 600 V143 Male 61 8.0 Non-Smoke V143 615 V137 Male 63 7.0 Non-Smoke V137 570 V136 Male 64 23.0 Non-Smoke V136 472 E Male 23 5.0 Non-Smoke JB67 D3E7 473 E Male 23 5.0 Non-Smoke BP31 A4C5 495 E Male 23 5.0 Non-Smoke JB67 D10D 497 E Male 23 5.0 Non-Smoke MF223 C7H 396 87ES Male 31 6.0 Non-Smoke 87ES3 404 88FG Male 39 4.0 Non-Smoke 88FG7 395 88FX Male 40 25.0 Non-Smoke 14 E1 283 13S Male 58 2.0 Non-Smoke #118 280 12S Male 59 5.0 Non-Smoke #117 263 Male 60 Non-Smoke #169 262 5S Male 70 13.0 Non-Smoke #105 254 3S Male 73 6.0 Non-Smoke #103 142 BC67 Female 35 15.0 Smoker BC67-18 370 34S Male 29 6.0 Smoker 34-30 374 34S Male 29 6.0 Smoker 34-45 375 437S Male 30 26.0 Non-Smoke 437-3 350 42S Male 56 6.0 Non-Smoke 42-32 371 42S Male 56 6.0 Non-Smoke 42-42 376 42S Male 56 6.0 Non-Smoke 42-9 451 89MA Male 19 4.0 Smoker 89MA4 461 90MX Male 33 10.0 Smoker 90MX5 426 89LN Male 39 6.0 Non-Smoke 89LN3 427 89LN Male 39 6.0 Non-Smoke 89LN1 449 88EZ Male 39 14.0 Smoker 88EZ4 452 89LX Male 41 12.0 Smoker 89LX2 301 4215H Male 22 22.0 Non-Smoke 4215B7 84 sf6.1 Female 20 8.0 Smoker 14 E1 78 sm6.1 Male 29 12.0 Smoker 24C9 239 sf27 Female 30 19.0 Smoker 17H8 232 nf39 Female 35 6.0 Non-Smoke 86F9 234 nf40 Female 41 12.0 Non-Smoke 8A6 165 sm47 Male 26 7.0 Smoker 66 E11 166 sm34 Male 26 6.0 Smoker 54B4 250 nm35 Male 27 3.0 Non-Smoke 59G4 152 nm91g Male 31 6.0 Non-Smoke 44B4 220 sm73 Male 36 10.0 Smoker 67B6 151 sm43 Male 37 18.0 Smoker 17 E4 246 sm41 Male 40 15.0 Smoker 68B12 210 sm95 Male 41 5.0 Smoker 34G10 249 sm62 Male 45 18.0 Smoker 44B10 340 325 Male 50 13.0 Smoker 325-2-16 755 1M0 Female 66 27.0 Non-Smoke 1M0-3 771 1M0 Female 66 27.0 Non-Smoke 1M0-15 774 1M0 Female 66 27.0 Non-Smoke 1M0-5 756 14M0 Female 70 33.0 Smoker 14M0-33 725 4M0 Male 55 78.0 Smoker 4M0-7 791 7M0 Male 62 34.0 Non-Smoke 7M0-7 36 16EO Female 75 18.0 Smoker 16E0-1 34 8EO Male 68 73.0 Smoker 8E0-11 30 15EO Male 83 15.0 Smoker 15E0-6 666 K34 Male 30 6.0 Non-Smoke K34 663 K30 Male 35 9.0 Non-Smoke K30 668 K30 Male 35 9.0 Non-Smoke K30 709 V135 Male 37 9.0 Non-Smoke V135 667 K36 Male 40 7.0 Non-Smoke K36 627 K27 Male 23 6.0 Non-Smoke K27 603 K26 Male 33 5.0 Non-Smoke K26 620 V123 Male 35
Load more

Recommended publications
  • DNA Insertion Mutations Can Be Predicted by a Periodic Probability
    Research article DNA insertion mutations can be predicted by a periodic probability function Tatsuaki Tsuruyama1 1Department of Pathology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan Running title: Probability prediction of mutation Correspondence to: Tatsuaki Tsuruyama Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan Tel.: +81-75-751-3488; Fax: +81-75-761-9591 E-mail: [email protected] 1 Abstract It is generally difficult to predict the positions of mutations in genomic DNA at the nucleotide level. Retroviral DNA insertion is one mode of mutation, resulting in host infections that are difficult to treat. This mutation process involves the integration of retroviral DNA into the host-infected cellular genomic DNA following the interaction between host DNA and a pre-integration complex consisting of retroviral DNA and integrase. Here, we report that retroviral insertion sites around a hotspot within the Zfp521 and N-myc genes can be predicted by a periodic function that is deduced using the diffraction lattice model. In conclusion, the mutagenesis process is described by a biophysical model for DNA–DNA interactions. Keywords: Insertion, mutagenesis, palindromic sequence, retroviral DNA 2 Text Introduction Extensive research has examined retroviral insertions to further our understanding of DNA mutations. Retrovirus-related diseases, including leukemia/lymphoma and AIDS, develop after retroviral genome insertion into the genomic DNA of the infected host cell. Retroviral DNA insertion is one of the modes of insertional mutation. After reverse-transcription of the retroviral genomic RNA into DNA, the retroviral DNA forms a pre-insertion complex (PIC) with the integrase enzyme, which catalyzes the insertion reaction.
    [Show full text]
  • DNA Sequence Insertion and Evolutionary Variation in Gene Regulation (Mobile Elements/Long Terminal Repeats/Alu Sequences/Factor-Binding Sites) Roy J
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 9374-9377, September 1996 Colloquium Paper This paper was presented at a colloquium entitled "Biology of Developmental Transcription Control, " organized by Eric H. Davidson, Roy J. Britten, and Gary Felsenfeld, held October 26-28, 1995, at the National Academy of Sciences in Irvine, CA. DNA sequence insertion and evolutionary variation in gene regulation (mobile elements/long terminal repeats/Alu sequences/factor-binding sites) RoY J. BRITrEN Division of Biology, California Institute of Technology, 101 Dahlia Avenue, Corona del Mar, CA 92625 ABSTRACT Current evidence on the long-term evolution- 3 and 4). Sequence change, obscuring the original structure, ary effect of insertion of sequence elements into gene regions has occurred in the long history, and the underlying rate of is reviewed, restricted to cases where a sequence derived from base substitution that is responsible is known (5). a past insertion participates in the regulation of expression of The requirements for a convincing example are: (i) that a useful gene. Ten such examples in eukaryotes demonstrate there be a trace of a known class of elements present in gene that segments of repetitive DNA or mobile elements have been region; (ii) that there is evidence that it has been there long inserted in the past in gene regions, have been preserved, enough to not just be a transient mutation; (iii) that some sometimes modified by selection, and now affect control of sequence residue of the mobile element or repeat participates transcription ofthe adjacent gene. Included are only examples in regulation of expression of the gene; (iv) that the gene have in which transcription control was modified by the insert.
    [Show full text]
  • Insertion Element (IS1 Insertion Sequence/Chloramphenicol Resistance Transposon Tn9/Integrative Recombination) L
    Proc. Nati. Acad. Sci. USA Vol. 75, No. 3, pp. 1490-1494, March 1978 Genetics Chromosomal integration of phage X by means of a DNA insertion element (IS1 insertion sequence/chloramphenicol resistance transposon Tn9/integrative recombination) L. A. MACHATTIE AND J. A. SHAPIRO Department of Microbiology, University of Chicago, Chicago, Illinois 60637 Communicated by Albert Dorfman, January 10, 1978 ABSTRACT Phage Xcamll2, which contains the chlor- carries a deletion of the gal-attB-bio region of the Escherichia amphenicol resistance transposon Tn9 and has a deletion of attP coil chromosome. MGBO is a gal+bio+ transductant of and the int gene, will lysogenize Escherichia coli K-12. Pro- phage integration occurs at different chromosomal sites, in- MADO. MS6 is a galE indicator for detection of XgalE + T- cluding lacYand maiB, but not at attB. All Xcamll2 prophages transducing particles and S1653 is a gal deletion strain for de- are excised from the chromosome after induction but with tection of Xgal + particles (3). Strain 200PS is a thi lacY strain various efficiencies for different locations. Heteroduplex from the Pasteur collection. Strain QL carries a complete lac analysis of XplacZ transducing phages isolated from a lacY:: deletion, strain X9003 carries the nonpolar M15 lacZ deletion, Xcamll2 prophage reveals an insertion sequence 1 (IS1) element and either will serve as indicator for XplacZ phage in a blue at theloint of viral and chromosomal DNA. Two lines of evi- dencekdicate that Xcamll2 encodes an excision activity that plaque assay (8). recognizes the ISI element: (i) prophage derepression increases Media. Our basic minimal medium and complete TYE the frequency of excision from IacYto yield lac+ revertants, and medium have been described (9).
    [Show full text]
  • Gene Therapy Glossary of Terms
    GENE THERAPY GLOSSARY OF TERMS A • Phase 3: A phase of research to describe clinical trials • Allele: one of two or more alternative forms of a gene that that gather more information about a drug’s safety and arise by mutation and are found at the same place on a effectiveness by studying different populations and chromosome. different dosages and by using the drug in combination • Adeno-Associated Virus: A single stranded DNA virus that has with other drugs. These studies typically involve more not been found to cause disease in humans. This type of virus participants.7 is the most frequently used in gene therapy.1 • Phase 4: A phase of research to describe clinical trials • Adenovirus: A member of a family of viruses that can cause occurring after FDA has approved a drug for marketing. infections in the respiratory tract, eye, and gastrointestinal They include post market requirement and commitment tract. studies that are required of or agreed to by the study • Adeno-Associated Virus Vector: Adeno viruses used as sponsor. These trials gather additional information about a vehicles for genes, whose core genetic material has been drug’s safety, efficacy, or optimal use.8 removed and replaced by the FVIII- or FIX-gene • Codon: a sequence of three nucleotides in DNA or RNA • Amino Acids: building block of a protein that gives instructions to add a specific amino acid to an • Antibody: a protein produced by immune cells called B-cells elongating protein in response to a foreign molecule; acts by binding to the • CRISPR: a family of DNA sequences that can be cleaved by molecule and often making it inactive or targeting it for specific enzymes, and therefore serve as a guide to cut out destruction and insert genes.
    [Show full text]
  • The Origin, Evolution, and Functional Impact of Short Insertion–Deletion Variants Identified in 179 Human Genomes
    Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Research The origin, evolution, and functional impact of short insertion–deletion variants identified in 179 human genomes Stephen B. Montgomery,1,2,3,14,16 David L. Goode,3,14,15 Erika Kvikstad,4,13,14 Cornelis A. Albers,5,6 Zhengdong D. Zhang,7 Xinmeng Jasmine Mu,8 Guruprasad Ananda,9 Bryan Howie,10 Konrad J. Karczewski,3 Kevin S. Smith,2 Vanessa Anaya,2 Rhea Richardson,2 Joe Davis,3 The 1000 Genomes Pilot Project Consortium, Daniel G. MacArthur,5,11 Arend Sidow,2,3 Laurent Duret,4 Mark Gerstein,8 Kateryna D. Makova,9 Jonathan Marchini,12 Gil McVean,12,13 and Gerton Lunter13,16 1–13[Author affiliations appear at the end of the paper.] Short insertions and deletions (indels) are the second most abundant form of human genetic variation, but our un- derstanding of their origins and functional effects lags behind that of other types of variants. Using population-scale sequencing, we have identified a high-quality set of 1.6 million indels from 179 individuals representing three diverse human populations. We show that rates of indel mutagenesis are highly heterogeneous, with 43%–48% of indels occurring in 4.03% of the genome, whereas in the remaining 96% their prevalence is 16 times lower than SNPs. Polymerase slippage can explain upwards of three-fourths of all indels, with the remainder being mostly simple de- letions in complex sequence. However, insertions do occur and are significantly associated with pseudo-palindromic sequence features compatible with the fork stalling and template switching (FoSTeS) mechanism more commonly as- sociated with large structural variations.
    [Show full text]
  • Glossary of Common Terms in Genetics
    Glossary of Common Terms in Genetics Acquired mutations Gene changes genetic information. DNA is held Multiplexing A sequencing approach that that arise within individual cells and together by weak bonds between base uses several pooled samples simultaneous­ accumulate throughout a person's life pairs of nucleotides: adenine, guanine, ly, greatly increasing sequencing speed. span. cytosine, and thymine. Mutation Any heritable change in DNA Alleles One of a group of genes that Gene The fundamental unit of heredi­ sequence. occur alternatively at a given locus. A ty. A gene is an ordered sequence of single allele is inherited separately from nucleotides located in a particular posi­ Nucleotide A subunit of DNA or RNA each parent (e.g., at a locus for eye tion on a particular chromosome that consisting of a nitrogenous base, a phos­ color, the allele might result in blue or encodes a specific functional product phate molecule, and a sugar molecule. brown eyes). (i.e., a protein or RNA molecule i. Thousands of nucleotides are linked to form a DNA or RNA molecule. Base pair Two nitrogenous bases (ade­ Gene expression The process by which nine and thymine or guanine and cyto- a gene's coded information is converted Oncogene One or more forms of a sine) held together by weak bonds. Two into the structures present and operat­ gene associated with cancer. strands of DNA are held together in the ing in the cell. shape of a double helix by the bonds Polygenic disorders Genetic disorders between base pairs. Gene mapping Determination of the resulting from the combined action of relative positions of genes on a DNA alleles of more than one gene (e.g., Carrier A person who has a recessive molecule and the distance between heart disease, diabetes, and some can­ mutated gene along with its normal them.
    [Show full text]
  • CRISPR-Cas9 DNA Base-Editing and Prime-Editing
    International Journal of Molecular Sciences Review CRISPR-Cas9 DNA Base-Editing and Prime-Editing Ariel Kantor 1,2,*, Michelle E. McClements 1,2 and Robert E. MacLaren 1,2 1 Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 9DU, UK 2 Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK * Correspondence: [email protected] Received: 14 July 2020; Accepted: 25 August 2020; Published: 28 August 2020 Abstract: Many genetic diseases and undesirable traits are due to base-pair alterations in genomic DNA. Base-editing, the newest evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based technologies, can directly install point-mutations in cellular DNA without inducing a double-strand DNA break (DSB). Two classes of DNA base-editors have been described thus far, cytosine base-editors (CBEs) and adenine base-editors (ABEs). Recently, prime-editing (PE) has further expanded the CRISPR-base-edit toolkit to all twelve possible transition and transversion mutations, as well as small insertion or deletion mutations. Safe and efficient delivery of editing systems to target cells is one of the most paramount and challenging components for the therapeutic success of BEs. Due to its broad tropism, well-studied serotypes, and reduced immunogenicity, adeno-associated vector (AAV) has emerged as the leading platform for viral delivery of genome editing agents, including DNA-base-editors. In this review, we describe the development of various base-editors, assess their technical advantages and limitations, and discuss their therapeutic potential to treat debilitating human diseases.
    [Show full text]
  • DNA Mutation Worksheetkey
    Name: ________________________ BIO300/CMPSC300 Mutation - Spring 2016 As you know from lecture, there are several types of mutation: DELETION (a base is lost) INSERTION (an extra base is inserted) Deletion and insertion may cause what’s called a FRAMESHIFT, meaning the reading “frame” changes, changing the amino acid sequence. POINT MUTATION (one base is substituted for another) If a point mutation changes the amino acid, it’s called a MISSENSE mutation. If a point mutation does not change the amino acid, it’s called a SILENT mutation. If a point mutation changes the amino acid to a “stop,” it’s called a NONSENSE mutation. Complete the boxes below. Classify each as either Deletion, Insertion, or Substitution AND as either frameshift, missense, silent or nonsense (hint: deletion or insertion will always be frameshift). Original DNA Sequence: T A C A C C T T G G C G A C G A C T mRNA Sequence: A U G U G G A A C C G C U G C U G A Amino Acid Sequence: MET -TRP- ASN - ARG- CYS - (STOP) Mutated DNA Sequence #1: T A C A T C T T G G C G A C G A C T What’s the mRNA sequence? A U G U A G A A C C G C U G C U G A What will be the amino acid sequence? MET -(STOP) Will there likely be effects? YES What kind of mutation is this? POINT MUTATION- NONSENSE Mutated DNA Sequence #2: T A C G A C C T T G G C G A C G A C T What’s the mRNA sequence? A U G C U G G A A C C G C U G C U G A What will be the amino acid sequence? MET - LEU -GLU– PRO-LEU-LEU Will there likely be effects? YES What kind of mutation is this? INSERTION - FRAME SHIFT Mutated DNA Sequence
    [Show full text]
  • Basic Molecular Genetics for Epidemiologists F Calafell, N Malats
    398 GLOSSARY Basic molecular genetics for epidemiologists F Calafell, N Malats ............................................................................................................................. J Epidemiol Community Health 2003;57:398–400 This is the first of a series of three glossaries on CHROMOSOME molecular genetics. This article focuses on basic Linear or (in bacteria and organelles) circular DNA molecule that constitutes the basic physical molecular terms. block of heredity. Chromosomes in diploid organ- .......................................................................... isms such as humans come in pairs; each member of a pair is inherited from one of the parents. general increase in the number of epide- Humans carry 23 pairs of chromosomes (22 pairs miological research articles that apply basic of autosomes and two sex chromosomes); chromo- science methods in their studies, resulting somes are distinguished by their length (from 48 A to 257 million base pairs) and by their banding in what is known as both molecular and genetic epidemiology, is evident. Actually, genetics has pattern when stained with appropriate methods. come into the epidemiological scene with plenty Homologous chromosome of new sophisticated concepts and methodologi- cal issues. Each of the chromosomes in a pair with respect to This fact led the editors of the journal to offer the other. Homologous chromosomes carry the you a glossary of terms commonly used in papers same set of genes, and recombine with each other applying genetic methods to health problems to during meiosis. facilitate your “walking” around the journal Sex chromosome issues and enjoying the articles while learning. Sex determining chromosome. In humans, as in Obviously, the topics are so extensive and inno- all other mammals, embryos carrying XX sex vative that a single short glossary would not be chromosomes develop as females, whereas XY sufficient to provide you with the minimum embryos develop as males.
    [Show full text]
  • The Transversion Pathway (Spontaneous Mutation/Acid Mutagenesis/Glycosidic Bond Migration) PAUL M
    Proc. Natl. Acad. Sci. USA Vol. 73, No. 11, pp. 4159-4163, November 1976 Genetics Heat mutagenesis in bacteriophage T4: The transversion pathway (spontaneous mutation/acid mutagenesis/glycosidic bond migration) PAUL M. BINGHAM, RICHARD H. BALTZ*, LYNN S. RIPLEY, AND JOHN W. DRAKEt Department of Microbiology, University of Illinois, Urbana, Ill. 61801 Communicated by Matthew S. Meselson, September 3, 1976 ABSTRACT Heat induces transversions (as well as transi- produce the homologous ochre (UAA) mutant and therefore tions) at GC base pairs in bacteriophage T4. The target base for go undetected, the heat-induced reversion of amber mutants transversions is guanine, which is converted to a product which could occur only by transversions at the G-C base pair (pro- is sometimes replicated and transcribed as a pyrimidine. A model for this process is proposed in which the deoxyguanosine ducing the tyrosine codons UAU or UAC). Table 2 shows that glycosidic bond migrates from N9 to N2: the resulting deoxy- amber mutants readily revert when heated. neoguanosine may pair with normal guanine to produce GC Amber mutants might, however, revert by extracistronic _ CG transversions. suppressors arising by G-C A-T transitions. Hydroxylamine specifically induces this transition, and a considerable number We have previously described the induction by heat of G-C - of amber mutants in the WI region have already been shown A-T transitions in bacteriophage T4 by deamination of cytosine to be refractory to hydroxylamine-induced reversion (3, 4). We to produce uracil (1). Earlier studies of heat mutagenesis in have extended this result by showing that the amber mutants bacteriophage T4 suggested that transversions were also in- described in Table 2 are also insusceptible to hydroxylamine- duced at G-C base pairs (2), and this conjecture is now con- induced reversion even when the treated stocks are grown firmed.
    [Show full text]
  • Recurrent De Novo Mutations in Neurodevelopmental Disorders: Properties and Clinical Implications Amy B
    Wilfert et al. Genome Medicine (2017) 9:101 DOI 10.1186/s13073-017-0498-x REVIEW Open Access Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications Amy B. Wilfert1†, Arvis Sulovari1†, Tychele N. Turner1, Bradley P. Coe1 and Evan E. Eichler1,2* Abstract Next-generation sequencing (NGS) is now more accessible to clinicians and researchers. As a result, our understanding of the genetics of neurodevelopmental disorders (NDDs) has rapidly advanced over the past few years. NGS has led to the discovery of new NDD genes with an excess of recurrent de novo mutations (DNMs) when compared to controls. Development of large-scale databases of normal and disease variation has given rise to metrics exploring the relative tolerance of individual genes to human mutation. Genetic etiology and diagnosis rates have improved, which have led to the discovery of new pathways and tissue types relevant to NDDs. In this review, we highlight several key findings based on the discovery of recurrent DNMs ranging from copy number variants to point mutations. We explore biases and patterns of DNM enrichment and the role of mosaicism and secondary mutations in variable expressivity. We discuss the benefit of whole-genome sequencing (WGS) over whole-exome sequencing (WES) to understand more complex, multifactorial cases of NDD and explain how this improved understanding aids diagnosis and management of these disorders. Comprehensive assessment of the DNM landscape across the genome using WGS and other technologies will lead to the development of novel functional and bioinformatics approaches to interpret DNMs and drive new insights into NDD biology.
    [Show full text]
  • Derived Neural Progenitor Cells Reveal Early Neurodevelopmental Phenotype for Koolen-De Vries Syndrome
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. https://hdl.handle.net/2066/226622 Please be advised that this information was generated on 2021-10-05 and may be subject to change. Modeling Neurodevelopmental Disorders Using Human Pluripotent Stem Cells: From Epigenetics Towards New Cellular Mechanisms Katrin Linda 1 Financial Support for printing this thesis was kindly provided by: Radboudumc Nijmegen Donders Institute for Brain, Cognition and Behaviour Cover design: Katrin Linda Lay-Out: Katrin Linda and Ridderprint B.V. (www.ridderprint.nl) Printed by: Ridderprint B.V. (www.ridderprint.nl) Copyright © 2020 by Katrin Linda All rights reserved. No parts of this publication may be reproduced or transmitted in any form or by any means without prior written permission of the author and holder of copyright. 2 Modeling Neurodevelopmental Disorders Using Human Pluripotent Stem Cells: From Epigenetics Towards New Cellular Mechanisms PROEFSCHRIFT ter verkrijging van graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. dr. J.H.J.M. van Krieken, volgens besluit van het college van decanen in het openbaar te verdedigen op woensdag 16 december 2020 om 14:30 uur precies door Katrin Linda geboren op 24 mei 1989 te Goch (Duitsland) 3 Promotoren Prof. dr. ir. J.H.L.M. van Bokhoven Dr. N. Nadif Kasri Copromotor Dr. B.B.A. de Vries Manuscriptcommissie Prof. dr. E.J.M. Storkebaum Dr. V.M. Heine (Amsterdam UMC) Prof. dr. Y.
    [Show full text]