Phenotypic Mutation 'Tropo' (pdf version)
AlleleTropo
Mutation Type missense
Chromosome9
Coordinate53,442,948 bp (GRCm39)
Base Change A ⇒ G (forward strand)
Gene Atm
Gene Name ataxia telangiectasia mutated
Synonym(s) C030026E19Rik
Chromosomal Location 53,350,449-53,448,040 bp (-) (GRCm39)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]
PHENOTYPE: Homozygotes for null mutations may exhibit locomotor abnormalities, motor learning deficits, growth retardation, sterility due to meiotic arrest, and susceptibility to thymic lymphomas. Mice homozygous for a kinase dead allele exhibit early embryonic lethality associated with genetic instability. [provided by MGI curators]
Accession Number

NCBI RefSeq: NM_007499; MGI:107202

MappedYes 
Amino Acid Change Isoleucine changed to Threonine
Institutional SourceBeutler Lab
Gene Model predicted gene model for protein(s): [ENSMUSP00000113388] [ENSMUSP00000115394] [ENSMUSP00000156344]
AlphaFold no structure available at present
SMART Domains Protein: ENSMUSP00000113388
Gene: ENSMUSG00000034218
AA Change: I105T

DomainStartEndE-ValueType
TAN 1 166 5.07e-68 SMART
low complexity region 431 445 N/A INTRINSIC
low complexity region 830 846 N/A INTRINSIC
low complexity region 929 940 N/A INTRINSIC
SCOP:d1gw5a_ 1039 1568 2e-4 SMART
coiled coil region 1615 1644 N/A INTRINSIC
low complexity region 1650 1662 N/A INTRINSIC
Pfam:FAT 2102 2499 4.4e-50 PFAM
low complexity region 2587 2599 N/A INTRINSIC
PI3Kc 2723 3026 1.11e-117 SMART
FATC 3034 3066 3.71e-11 SMART
Predicted Effect probably damaging

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
(Using ENSMUST00000118282)
SMART Domains Protein: ENSMUSP00000115394
Gene: ENSMUSG00000034218
AA Change: I87T

DomainStartEndE-ValueType
TAN 1 140 2.88e-40 SMART
Predicted Effect probably damaging

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
(Using ENSMUST00000150244)
Predicted Effect probably damaging

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
(Using ENSMUST00000232179)
Meta Mutation Damage Score 0.7173 question?
Is this an essential gene? Probably essential (E-score: 0.905) question?
Phenotypic Category Unknown
Candidate Explorer Status loading ...
Single pedigree
Linkage Analysis Data
Penetrance  
Alleles Listed at MGI

All Mutations and Alleles(38) : Chemically induced (ENU)(2) Gene trapped(19) Targeted(17)

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00090:Atm APN 9 53435743 missense probably damaging 1.00
IGL00466:Atm APN 9 53410412 splice site probably benign
IGL00567:Atm APN 9 53414416 nonsense probably null
IGL00702:Atm APN 9 53423131 missense probably benign 0.02
IGL00743:Atm APN 9 53424416 missense probably benign 0.00
IGL00771:Atm APN 9 53404354 missense probably benign 0.01
IGL00773:Atm APN 9 53433444 missense probably benign 0.00
IGL00819:Atm APN 9 53429831 missense probably damaging 1.00
IGL00864:Atm APN 9 53445233 missense probably damaging 0.99
IGL00985:Atm APN 9 53371116 missense probably damaging 0.98
IGL01109:Atm APN 9 53401593 missense probably damaging 1.00
IGL01120:Atm APN 9 53372422 critical splice acceptor site probably null
IGL01369:Atm APN 9 53426617 missense probably benign
IGL01374:Atm APN 9 53443024 missense possibly damaging 0.58
IGL01406:Atm APN 9 53351046 makesense probably null
IGL01409:Atm APN 9 53410471 missense probably benign 0.01
IGL01434:Atm APN 9 53419107 missense probably benign 0.04
IGL01486:Atm APN 9 53421513 missense probably benign
IGL01583:Atm APN 9 53395547 splice site probably benign
IGL01861:Atm APN 9 53405912 missense probably null 0.89
IGL01865:Atm APN 9 53372302 missense probably damaging 1.00
IGL02026:Atm APN 9 53353717 splice site probably null
IGL02072:Atm APN 9 53371096 missense probably benign 0.01
IGL02075:Atm APN 9 53438537 missense probably damaging 1.00
IGL02127:Atm APN 9 53399283 missense probably damaging 1.00
IGL02175:Atm APN 9 53391965 missense probably damaging 0.99
IGL02246:Atm APN 9 53438485 missense probably benign 0.12
IGL02259:Atm APN 9 53429794 splice site probably benign
IGL02351:Atm APN 9 53433476 missense probably benign 0.04
IGL02358:Atm APN 9 53433476 missense probably benign 0.04
IGL02387:Atm APN 9 53391066 splice site probably null
IGL02417:Atm APN 9 53390995 missense probably benign 0.00
IGL02422:Atm APN 9 53412092 missense probably damaging 1.00
IGL02445:Atm APN 9 53365630 missense probably benign 0.00
IGL02492:Atm APN 9 53367159 missense probably damaging 0.99
IGL02513:Atm APN 9 53408562 splice site probably benign
IGL02633:Atm APN 9 53359453 missense probably damaging 1.00
IGL02634:Atm APN 9 53427863 missense probably benign 0.00
IGL02948:Atm APN 9 53364740 splice site probably benign
IGL02959:Atm APN 9 53382718 missense probably damaging 1.00
IGL02965:Atm APN 9 53364863 missense probably damaging 1.00
IGL03085:Atm APN 9 53395471 missense possibly damaging 0.89
antebellum UTSW 9 53429859 nonsense probably null
bull_run UTSW 9 53399222 missense probably benign 0.09
Civil UTSW 9 53403568 missense possibly damaging 0.78
gettysburg UTSW 9 53367288 splice site probably null
Grant UTSW 9 53423217 nonsense probably null
Indicative UTSW 9 53356676 splice site probably null
Marker UTSW 9 53365579 splice site probably benign
maunder UTSW 9 53410497 nonsense probably null
mockingbird UTSW 9 53427767 nonsense probably null
mockingbird2 UTSW 9 53399887 missense probably damaging 1.00
osphere UTSW 9 53390973 missense probably damaging 0.99
shiloh UTSW 9 53376598 missense probably damaging 1.00
Strato UTSW 9 53414318 missense probably damaging 1.00
thrasher UTSW 9 53356807 missense probably benign 0.01
P0019:Atm UTSW 9 53376328 splice site probably benign
PIT4403001:Atm UTSW 9 53412282 missense probably benign
PIT4687001:Atm UTSW 9 53398112 critical splice donor site probably null
R0004:Atm UTSW 9 53364828 splice site probably benign
R0035:Atm UTSW 9 53424480 missense probably benign 0.01
R0098:Atm UTSW 9 53429869 missense probably benign 0.10
R0098:Atm UTSW 9 53429869 missense probably benign 0.10
R0201:Atm UTSW 9 53365579 splice site probably benign
R0304:Atm UTSW 9 53427644 missense probably benign 0.34
R0308:Atm UTSW 9 53365773 splice site probably null
R0362:Atm UTSW 9 53370138 missense possibly damaging 0.90
R0470:Atm UTSW 9 53372266 missense probably damaging 1.00
R0513:Atm UTSW 9 53415248 missense probably benign 0.00
R0589:Atm UTSW 9 53401492 missense possibly damaging 0.51
R0617:Atm UTSW 9 53370241 nonsense probably null
R0630:Atm UTSW 9 53442922 splice site probably benign
R0652:Atm UTSW 9 53397314 missense probably damaging 0.98
R0698:Atm UTSW 9 53426539 missense probably damaging 1.00
R0737:Atm UTSW 9 53367866 missense probably damaging 1.00
R0885:Atm UTSW 9 53371123 missense probably benign
R0947:Atm UTSW 9 53415392 missense probably benign 0.01
R0948:Atm UTSW 9 53407258 missense probably benign
R1144:Atm UTSW 9 53422998 splice site probably benign
R1252:Atm UTSW 9 53367140 missense probably damaging 1.00
R1295:Atm UTSW 9 53367830 missense probably damaging 1.00
R1296:Atm UTSW 9 53367830 missense probably damaging 1.00
R1419:Atm UTSW 9 53368789 missense probably benign 0.00
R1477:Atm UTSW 9 53375573 missense probably benign 0.00
R1596:Atm UTSW 9 53364678 missense probably damaging 1.00
R1630:Atm UTSW 9 53390973 missense probably damaging 0.99
R1667:Atm UTSW 9 53412232 missense probably damaging 1.00
R1681:Atm UTSW 9 53433455 missense possibly damaging 0.94
R1703:Atm UTSW 9 53412000 missense probably benign
R1817:Atm UTSW 9 53403533 splice site probably benign
R1840:Atm UTSW 9 53367830 missense probably damaging 1.00
R1848:Atm UTSW 9 53379312 missense probably benign 0.06
R1906:Atm UTSW 9 53417868 missense probably damaging 1.00
R1958:Atm UTSW 9 53382718 missense probably damaging 1.00
R2108:Atm UTSW 9 53355297 missense probably damaging 1.00
R2116:Atm UTSW 9 53412269 missense probably benign 0.36
R2134:Atm UTSW 9 53379264 critical splice donor site probably null
R2137:Atm UTSW 9 53364675 missense probably damaging 1.00
R2291:Atm UTSW 9 53402209 splice site probably null
R2348:Atm UTSW 9 53403568 missense possibly damaging 0.78
R2483:Atm UTSW 9 53421566 missense probably damaging 1.00
R2567:Atm UTSW 9 53368770 missense possibly damaging 0.72
R2897:Atm UTSW 9 53419105 missense probably damaging 0.99
R2939:Atm UTSW 9 53406011 missense probably damaging 1.00
R3008:Atm UTSW 9 53392050 missense probably benign 0.00
R3236:Atm UTSW 9 53391048 missense probably benign 0.15
R3847:Atm UTSW 9 53414375 missense possibly damaging 0.94
R3889:Atm UTSW 9 53417936 splice site probably benign
R3919:Atm UTSW 9 53403578 missense probably benign 0.00
R4125:Atm UTSW 9 53361921 missense probably damaging 1.00
R4222:Atm UTSW 9 53391969 missense probably benign
R4395:Atm UTSW 9 53376527 missense probably benign 0.09
R4466:Atm UTSW 9 53359469 nonsense probably null
R4502:Atm UTSW 9 53407246 missense possibly damaging 0.92
R4514:Atm UTSW 9 53404339 missense probably damaging 0.99
R4528:Atm UTSW 9 53412059 missense probably benign 0.39
R4593:Atm UTSW 9 53364894 missense possibly damaging 0.55
R4627:Atm UTSW 9 53367806 missense possibly damaging 0.79
R4634:Atm UTSW 9 53443033 missense probably benign 0.01
R4665:Atm UTSW 9 53375529 missense probably benign 0.00
R4672:Atm UTSW 9 53433501 missense probably damaging 0.99
R4741:Atm UTSW 9 53364907 missense probably benign 0.10
R4808:Atm UTSW 9 53356795 missense probably damaging 0.99
R4959:Atm UTSW 9 53426601 missense probably benign
R4996:Atm UTSW 9 53435807 missense probably benign 0.09
R5030:Atm UTSW 9 53431409 nonsense probably null
R5214:Atm UTSW 9 53402327 missense probably benign 0.09
R5260:Atm UTSW 9 53417911 missense probably damaging 0.99
R5311:Atm UTSW 9 53429923 missense probably benign 0.00
R5394:Atm UTSW 9 53419077 critical splice donor site probably null
R5400:Atm UTSW 9 53414318 missense probably damaging 1.00
R5436:Atm UTSW 9 53371104 missense probably benign 0.00
R5441:Atm UTSW 9 53427767 nonsense probably null
R5569:Atm UTSW 9 53427750 nonsense probably null
R5856:Atm UTSW 9 53407255 missense possibly damaging 0.64
R5891:Atm UTSW 9 53408459 missense probably benign
R5910:Atm UTSW 9 53359380 missense probably damaging 0.96
R6054:Atm UTSW 9 53371173 missense probably damaging 1.00
R6062:Atm UTSW 9 53399887 missense probably damaging 1.00
R6092:Atm UTSW 9 53435714 missense probably damaging 1.00
R6127:Atm UTSW 9 53435809 missense probably damaging 1.00
R6160:Atm UTSW 9 53402259 missense probably benign 0.04
R6267:Atm UTSW 9 53355300 missense probably damaging 1.00
R6273:Atm UTSW 9 53399222 missense probably benign 0.09
R6284:Atm UTSW 9 53356676 splice site probably null
R6478:Atm UTSW 9 53401554 missense probably damaging 1.00
R6547:Atm UTSW 9 53351457 missense probably damaging 1.00
R6549:Atm UTSW 9 53404477 missense probably benign 0.00
R6704:Atm UTSW 9 53370153 missense probably benign 0.02
R6715:Atm UTSW 9 53442948 missense probably damaging 1.00
R6737:Atm UTSW 9 53397351 missense probably benign 0.30
R6759:Atm UTSW 9 53429859 nonsense probably null
R6766:Atm UTSW 9 53401582 missense probably damaging 0.99
R6813:Atm UTSW 9 53408535 missense probably benign 0.00
R6852:Atm UTSW 9 53393730 missense possibly damaging 0.93
R7064:Atm UTSW 9 53419181 missense probably benign 0.02
R7208:Atm UTSW 9 53423308 splice site probably null
R7211:Atm UTSW 9 53399860 missense probably benign 0.01
R7220:Atm UTSW 9 53423217 nonsense probably null
R7336:Atm UTSW 9 53373803 missense possibly damaging 0.47
R7363:Atm UTSW 9 53376598 missense probably damaging 1.00
R7378:Atm UTSW 9 53364737 critical splice acceptor site probably null
R7472:Atm UTSW 9 53359425 missense possibly damaging 0.81
R7487:Atm UTSW 9 53435654 missense probably benign
R7497:Atm UTSW 9 53423191 missense probably benign 0.00
R7584:Atm UTSW 9 53424427 missense probably damaging 0.99
R7624:Atm UTSW 9 53366068 missense probably damaging 0.99
R7653:Atm UTSW 9 53401602 nonsense probably null
R7660:Atm UTSW 9 53356807 missense probably benign 0.01
R7679:Atm UTSW 9 53353797 missense probably damaging 1.00
R7720:Atm UTSW 9 53433539 missense possibly damaging 0.54
R8221:Atm UTSW 9 53367288 splice site probably null
R8247:Atm UTSW 9 53361870 missense
R8334:Atm UTSW 9 53433573 missense probably benign 0.00
R8503:Atm UTSW 9 53399352 missense probably damaging 0.99
R8552:Atm UTSW 9 53435797 missense probably damaging 1.00
R8749:Atm UTSW 9 53410497 nonsense probably null
R8838:Atm UTSW 9 53427851 missense probably damaging 0.99
R9126:Atm UTSW 9 53370134 missense probably benign 0.01
R9131:Atm UTSW 9 53445044 missense probably benign 0.10
R9191:Atm UTSW 9 53438590 missense probably benign 0.29
R9257:Atm UTSW 9 53407150 critical splice donor site probably null
R9473:Atm UTSW 9 53410272 missense probably benign
R9558:Atm UTSW 9 53412081 missense probably benign 0.00
R9598:Atm UTSW 9 53431381 missense probably benign 0.34
R9717:Atm UTSW 9 53427817 missense probably damaging 1.00
R9794:Atm UTSW 9 53429867 missense probably benign
X0067:Atm UTSW 9 53390994 missense probably benign 0.00
Z1088:Atm UTSW 9 53442987 missense probably damaging 1.00
Mode of Inheritance Unknown
Local Stock
Repository
Last Updated 2020-12-09 6:46 AM by External Program
Record Created 2019-02-01 7:40 AM by Bruce Beutler
Record Posted 2019-02-08
Phenotypic Description

Figure 1. Tropo mice exhibit increased frequencies of B1a cells in B1 cells. Flow cytometric analysis of peripheral blood was utilized to determine B1a cell frequency. Normalized data are shown. Abbreviations: WT, wild-type; REF, homozygous reference mice; HET, heterozygous variant mice; VAR, homozygous variant mice. Mean (μ) and standard deviation (σ) are indicated.

Figure 2. Tropo mice exhibit increased frequencies of macrophages. Flow cytometric analysis of peripheral blood was utilized to determine macrophage frequency. Normalized data are shown. Abbreviations: WT, wild-type; REF, homozygous reference mice; HET, heterozygous variant mice; VAR, homozygous variant mice. Mean (μ) and standard deviation (σ) are indicated.

The tropo phenotype was identified among N-ethyl-N-nitrosourea (ENU)-mutagenized G3 mice of the pedigree R6715, some of which showed increased frequencies of B1a cells in B1 cells (Figure 1) and macrophages (Figure 2) in the peripheral blood.

Nature of Mutation

Figure 3. Linkage mapping of the increased macrophage frequency using a recessive model of inheritance. Manhattan plot shows -log10 P values (Y-axis) plotted against the chromosome positions of 33 mutations (X-axis) identified in the G1 male of pedigree R6715. Normalized phenotype data are shown for single locus linkage analysis without consideration of G2 dam identity. Horizontal pink and red lines represent thresholds of P = 0.05, and the threshold for P = 0.05 after applying Bonferroni correction, respectively.

Whole exome HiSeq sequencing of the G1 grandsire identified 33 mutations. Both of the above anomalies were linked by continuous variable mapping to mutations in two genes on chromosome 9: Pgr and Atm. The mutation in Atm was presumed causative as the immune phenotypes observed in tropo mice mimics that of other mice expressing mutant Atm alleles (see MGI). The mutation in Atm is a T to C transition at base pair 53,531,648 (v38) on chromosome 9, or base pair 5,169 in the GenBank genomic region NC_000075. The strongest association was found with a recessive model of inheritance to the macrophage phenotype, wherein one variant homozygote departed phenotypically from eight homozygous reference mice and 13 heterozygous mice with a P value of 1.718 x 10-25  (Figure 3).  

The mutation corresponds to residue 453 in the mRNA sequence NM_007499 within exon 4 of 64 total exons.


 
437 TTGGTCAGATACTTCATCAAATGTGCAAACAAA

100 -L--V--R--Y--F--I--K--C--A--N--K-


 

The mutated nucleotide is indicated in red. The mutation results in an isoleucine to threonine substitution at amino acid 105 (I105T) in the ATM protein, and is strongly predicted by PolyPhen-2 to be damaging (score = 1.000).

Illustration of Mutations in
Gene & Protein
Protein Prediction

Figure 4. Domain organization of ATM. The location of the tropo mutation is indicated. Mutations found in ATM are noted in red. Click on each mutation to view more information.

ATM (ataxia telangiectasia mutated) is a member of the PI3/PI4-kinase (PIKK) family. The PIKK family members DNA-PKCS (DNA-dependent protein kinase; see clover), ATR (ATM and Rad3-related), and ATM are involved in DNA repair [(1); reviewed in (2)]. A 250-amino acid region at the C-terminus of ATM constitutes the catalytic PIKK domain (Figure 4). The PIKK domain is flanked by the FAT domain (named for its homology to FRAP, ATM and TRRAP) and a FATC domain (FAT at the extreme C-terminus). The FAT and FATC domains occur in combination in all PIKK family members, suggesting a possible role in maintaining a structural conformation essential for the activation of the catalytic site (3;4). The FAT domain mediates ATM dimerization and has three tetratriocpeptide repeat domains (TRDs). The N-terminal portion of the protein up to the FAT domain consists of HEAT (Huntingtin, Elongation factor 3, A subunit of protein phosphatase 2A and TOR1) repeats (5). HEAT repeats are helical structural repeats that mediate protein-protein interactions (6).

The tropo mutation results in an isoleucine to threonine substitution at amino acid 105 (I105T); amino acid 105 is within the HEAT repeat region.

For more information about Atm, please see the record for mockingbird.

Putative Mechanism

ATM is a cell cycle checkpoint kinase that phosphorylates proteins in several cell processes, including DNA repair, apoptosis, cell cycle checkpoints, telomere dysfunction, translation initiation, gene regulation, mitosis, and hypoxia. In all, there are 900 putative ATM/ATR phosphorylation sites on over 700 proteins in the DNA damage response (DDR) pathway alone (7).

Mutations in human ATM are linked to ataxia-telangiectasia [OMIM: #208900; (8;9)] and susceptibility to breast cancer (OMIM: #114480) as well as somatic B-cell non-Hodgkin lymphoma, somatic mantle cell lymphoma, and somatic T-cell prolymphocytic leukemia. Ataxia-telangiectasia is characterized by progressive cerebellar ataxia due to premature degeneration of Purkinje and granule cells, telangiectasia (dilated blood vessels), growth retardation, gonadal atrophy, immune defects, and a predisposition to malignancy (lymphoma, leukemia, and breast cancer). Fibroblasts from ataxia-telangiectasia patients exhibit aberrant gross morphology and cytoskeletal organization, poor cell growth, defective cell-cycle checkpoints, telomere loss, and chromosome end-to-end associations.

Atm­-deficient (Atm-/-) mice exhibited reduced body weights, increased incidence of T-cell-derived lymphoma, premature death (median survival is 113 days), reduced numbers of CD4+ and CD8+ T cells, reduced numbers of CD3/CD4 and CD3/CD8 T cells, reduced numbers of active T cells, reduced numbers of pre-B cells, reduced levels of IgG, male and female infertility, hypoactivity, impaired coordination, impaired glucose tolerance, and insulin resistance (10-18). B cells from the Atm-/- mice exhibited reduced class switch recombination with increased genomic instability after tamoxifen treatment compared to cells from wild-type mice (19). Homozygous mice expressing a kinase dead mutant Atm allele exhibited embryonic lethality from embryonic day (E) 9.5 to E10.5 (19). Homozygous mice expressing a mutant Atm allele (a 9 base pair in-frame deletion in exon 54 resulting in deletion of Ser2556-Arg2557-Iso2558 in the protein) exhibited premature death by 40 weeks of age (50%), reduced body size, increased tumor incidence, increased numbers of double-negative and single-positive T cells, reduced thymocyte numbers, and male infertility (16). The phenotype of the tropo mice indicates loss of ATM-associated function.

Primers PCR Primer
Tropo_pcr_F: GCTACGCTAACTCCTGAAGC
Tropo_pcr_R: ACAAGAGATTGTTTCATGTGTCTGG

Sequencing Primer
Tropo_seq_F: ACGCTAACTCCTGAAGCATTTGTG
Tropo_seq_R: TGGTACAACAGTGTGGTTTAAAAG
Genotyping

PCR program

1) 94°C 2:00
2) 94°C 0:30
3) 55°C 0:30
4) 72°C 1:00
5) repeat steps (2-4) 40x
6) 72°C 10:00
7) 4°C hold


The following sequence of 511 nucleotides is amplified (chromosome 9, - strand):


1   acaagagatt gtttcatgtg tctggttggt acaacagtgt ggtttaaaag atgttttggg
61  ggaagataca caggagtttt tgaagtgata aaagtataag cattaatgag gatatgattt
121 atttttcctt gaaggttttt acagaagtac attcaaaaag aaatggaaag tctgagaaca
181 gcaaaatcaa atgtatcagc caccacacag agctccagac agaagaagat gcaagagatc
241 agcagtttgg tcagatactt catcaaatgt gcaaacaaaa gtaagtaacc ttggctgcgt
301 gtggtggcac acactgctgt ggtggcgcac acctttagtc ccagcactca aaaggcagag
361 gcaggtggat ctatagccta gcctggacta tagagtgagt tccaggacag ccagggctac
421 acagagaaac cctgcctcaa aaaacccaaa gcaacaaaaa acgtaaacaa catcatgtat
481 tacacacaaa tgcttcagga gttagcgtag c


Primer binding sites are underlined and the sequencing primers are highlighted; the mutated nucleotide is shown in red.

References
Science Writers Anne Murray
Illustrators Diantha La Vine
AuthorsXue Zhong, Jin Huk Choi, and Bruce Beutler