Mutagenetix > Incidental Mutation

Incidental Mutation 'R0050:Pear1'

16144

Institutional Source

Beutler Lab

Gene Symbol

Pear1

Ensembl Gene

ENSMUSG00000028073

Gene Name

platelet endothelial aggregation receptor 1

Synonyms

Jedi-1, 3110045G13Rik

MMRRC Submission

038344-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0050 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

87656404-87676262 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

G to T at 87663294 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 441 (Y441*)

Ref Sequence

ENSEMBL: ENSMUSP00000133323 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029714] [ENSMUST00000079083] [ENSMUST00000090981] [ENSMUST00000172590] [ENSMUST00000172621] [ENSMUST00000174759] [ENSMUST00000174713] [ENSMUST00000174267] [ENSMUST00000174219] [ENSMUST00000173468] [ENSMUST00000173184] [ENSMUST00000173225] [ENSMUST00000174776]

AlphaFold

Q8VIK5

Predicted Effect

probably null
Transcript: ENSMUST00000029714
AA Change: Y441*

SMART Domains

Protein: ENSMUSP00000029714
Gene: ENSMUSG00000028073
AA Change: Y441*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
low complexity region	67	78	N/A	INTRINSIC
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF_like	146	185	1.92e0	SMART
EGF_like	189	246	1.99e0	SMART
EGF	217	258	1.04e1	SMART
EGF_Lam	274	313	1.21e-4	SMART
EGF	312	344	4.03e-1	SMART
EGF_Lam	361	402	1.33e-1	SMART
EGF	401	433	1.18e-2	SMART
EGF_like	449	488	1.72e0	SMART
EGF	487	519	6.92e0	SMART
EGF_Lam	535	574	2.08e-3	SMART
EGF	573	605	5.49e-3	SMART
EGF_Lam	620	660	1.58e-3	SMART
EGF	659	691	3.1e-2	SMART
EGF	702	734	2.53e1	SMART
transmembrane domain	754	776	N/A	INTRINSIC
low complexity region	809	822	N/A	INTRINSIC
low complexity region	829	835	N/A	INTRINSIC
low complexity region	954	971	N/A	INTRINSIC
low complexity region	993	1002	N/A	INTRINSIC
low complexity region	1019	1031	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000079083
AA Change: Y441*

SMART Domains

Protein: ENSMUSP00000078090
Gene: ENSMUSG00000028073
AA Change: Y441*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
low complexity region	67	78	N/A	INTRINSIC
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF_like	146	185	1.92e0	SMART
EGF_like	189	246	1.99e0	SMART
EGF	217	258	1.04e1	SMART
EGF_Lam	274	313	1.21e-4	SMART
EGF	312	344	4.03e-1	SMART
EGF_Lam	361	402	1.33e-1	SMART
EGF	401	433	1.18e-2	SMART
EGF_like	449	488	1.72e0	SMART
EGF	487	519	6.92e0	SMART
EGF_Lam	535	574	2.08e-3	SMART
EGF	573	605	5.49e-3	SMART
EGF_Lam	620	660	1.58e-3	SMART
EGF	659	691	3.1e-2	SMART
EGF	702	734	2.53e1	SMART
transmembrane domain	754	776	N/A	INTRINSIC
low complexity region	809	822	N/A	INTRINSIC
low complexity region	829	835	N/A	INTRINSIC
low complexity region	954	971	N/A	INTRINSIC
low complexity region	993	1002	N/A	INTRINSIC
low complexity region	1019	1031	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000090981
AA Change: Y441*

SMART Domains

Protein: ENSMUSP00000088503
Gene: ENSMUSG00000028073
AA Change: Y441*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
low complexity region	67	78	N/A	INTRINSIC
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF_like	146	185	1.92e0	SMART
EGF_like	189	246	1.99e0	SMART
EGF	217	258	1.04e1	SMART
EGF_Lam	274	313	1.21e-4	SMART
EGF	312	344	4.03e-1	SMART
EGF_Lam	361	402	1.33e-1	SMART
EGF	401	433	1.18e-2	SMART
EGF_like	449	488	1.72e0	SMART
EGF	487	519	6.92e0	SMART
EGF_Lam	535	574	2.08e-3	SMART
EGF	573	605	5.49e-3	SMART
EGF_Lam	620	660	1.58e-3	SMART
EGF	659	691	3.1e-2	SMART
EGF	702	734	2.53e1	SMART
transmembrane domain	754	776	N/A	INTRINSIC
low complexity region	809	822	N/A	INTRINSIC
low complexity region	829	835	N/A	INTRINSIC
low complexity region	954	971	N/A	INTRINSIC
low complexity region	993	1002	N/A	INTRINSIC
low complexity region	1019	1031	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000172590

SMART Domains

Protein: ENSMUSP00000133480
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
Blast:EGF	23	50	8e-13	BLAST

Predicted Effect

probably null
Transcript: ENSMUST00000172621
AA Change: Y441*

SMART Domains

Protein: ENSMUSP00000133474
Gene: ENSMUSG00000028073
AA Change: Y441*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
low complexity region	67	78	N/A	INTRINSIC
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF_like	146	185	1.92e0	SMART
EGF_like	189	246	1.99e0	SMART
EGF	217	258	1.04e1	SMART
EGF_Lam	274	313	1.21e-4	SMART
EGF	312	344	4.03e-1	SMART
EGF_Lam	361	402	1.33e-1	SMART
EGF	401	433	1.18e-2	SMART
EGF_like	449	488	1.72e0	SMART
EGF	487	519	6.92e0	SMART
EGF_Lam	535	574	2.08e-3	SMART
EGF	573	605	5.49e-3	SMART
EGF_Lam	620	660	1.58e-3	SMART
EGF	659	691	3.1e-2	SMART
EGF	702	734	2.53e1	SMART
transmembrane domain	754	776	N/A	INTRINSIC
low complexity region	809	822	N/A	INTRINSIC
low complexity region	829	835	N/A	INTRINSIC
low complexity region	954	971	N/A	INTRINSIC
low complexity region	993	1002	N/A	INTRINSIC
low complexity region	1019	1031	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000172631

Predicted Effect

probably benign
Transcript: ENSMUST00000172669

SMART Domains

Protein: ENSMUSP00000134451
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
EGF_like	1	34	1.85e0	SMART
EGF	33	65	3.1e-2	SMART
EGF	76	108	2.53e1	SMART
transmembrane domain	128	150	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000174759
AA Change: Y441*

SMART Domains

Protein: ENSMUSP00000133323
Gene: ENSMUSG00000028073
AA Change: Y441*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
low complexity region	67	78	N/A	INTRINSIC
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF_like	146	185	1.92e0	SMART
EGF_like	189	246	1.99e0	SMART
EGF	217	258	1.04e1	SMART
EGF_Lam	274	313	1.21e-4	SMART
EGF	312	344	4.03e-1	SMART
EGF_Lam	361	402	1.33e-1	SMART
EGF	401	433	1.18e-2	SMART
EGF_like	449	488	1.72e0	SMART
EGF	487	519	6.92e0	SMART
EGF_Lam	535	574	2.08e-3	SMART
EGF	573	605	5.49e-3	SMART
EGF_Lam	620	660	1.58e-3	SMART
EGF	659	691	3.1e-2	SMART
EGF	702	734	2.53e1	SMART
transmembrane domain	754	776	N/A	INTRINSIC
low complexity region	809	822	N/A	INTRINSIC
low complexity region	829	835	N/A	INTRINSIC
low complexity region	954	971	N/A	INTRINSIC
low complexity region	993	1002	N/A	INTRINSIC
low complexity region	1019	1031	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000173490

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000173747

Predicted Effect

probably benign
Transcript: ENSMUST00000174713

SMART Domains

Protein: ENSMUSP00000134215
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174267

SMART Domains

Protein: ENSMUSP00000133626
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174219

SMART Domains

Protein: ENSMUSP00000133565
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
EGF	15	47	4.03e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000173468

SMART Domains

Protein: ENSMUSP00000133988
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
Pfam:EMI	23	96	2.1e-16	PFAM
EGF	102	130	3.82e-2	SMART
EGF_like	132	173	2.92e1	SMART
EGF	184	215	1.84e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000173184

SMART Domains

Protein: ENSMUSP00000134100
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
Pfam:EMI	23	95	3.5e-17	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000173225

SMART Domains

Protein: ENSMUSP00000134387
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174776

SMART Domains

Protein: ENSMUSP00000133749
Gene: ENSMUSG00000028073

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
Pfam:EMI	23	96	6.3e-17	PFAM
Blast:FU	97	120	1e-5	BLAST

Meta Mutation Damage Score

0.9708

Coding Region Coverage

1x: 88.6%
3x: 85.4%
10x: 76.7%
20x: 62.7%

Validation Efficiency

90% (86/96)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] PEAR1 is a platelet receptor that signals upon the formation of platelet-platelet contacts independent of platelet activation and secondary to platelet aggregation (Nanda et al., 2005 [PubMed 15851471]).[supplied by OMIM, Mar 2008]
PHENOTYPE: Mice homozygous for a knock-out allele show no apparent defects in hemostasis or thrombus formation. Although in vitro dextran sulfate-induced platelet aggregation is impaired, platelet aggregation initiated with physiological agonists is normal. [provided by MGI curators]

Allele List at MGI

All alleles(3) : Targeted(2) Gene trapped(1)

Other mutations in this stock

Total: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca1	A	G	4: 53,069,910 (GRCm39)		probably benign	Het
Abca9	C	T	11: 110,036,417 (GRCm39)	C564Y	probably damaging	Het
Abhd14a	A	T	9: 106,318,082 (GRCm39)		probably benign	Het
Acnat2	G	A	4: 49,380,586 (GRCm39)	T264I	probably benign	Het
Adamts2	T	C	11: 50,666,222 (GRCm39)	V406A	probably damaging	Het
Adcy5	A	G	16: 35,124,673 (GRCm39)		probably benign	Het
Akr1c13	T	C	13: 4,244,669 (GRCm39)		probably benign	Het
Ankar	T	A	1: 72,695,323 (GRCm39)	E1093D	probably damaging	Het
Arhgef38	C	A	3: 132,837,957 (GRCm39)	D75Y	probably damaging	Het
Asns	T	C	6: 7,676,019 (GRCm39)	I484V	probably benign	Het
Astn1	T	C	1: 158,407,294 (GRCm39)		probably benign	Het
Atg4b	T	A	1: 93,715,440 (GRCm39)		probably benign	Het
Cadm2	A	G	16: 66,750,154 (GRCm39)		probably benign	Het
Ces2c	T	A	8: 105,574,831 (GRCm39)	M96K	probably benign	Het
Cpd	T	A	11: 76,683,685 (GRCm39)	T1025S	possibly damaging	Het
Daw1	T	C	1: 83,158,086 (GRCm39)	V45A	probably benign	Het
Dmrt3	C	A	19: 25,599,953 (GRCm39)	P266H	probably damaging	Het
Dnah10	A	G	5: 124,907,808 (GRCm39)	T4416A	probably benign	Het
Dock9	A	G	14: 121,844,637 (GRCm39)	V1124A	probably benign	Het
Ermp1	C	A	19: 29,606,184 (GRCm39)	A190S	probably damaging	Het
Gm10267	T	A	18: 44,289,520 (GRCm39)		probably benign	Het
Golga2	T	A	2: 32,182,139 (GRCm39)	V29D	probably damaging	Het
Gprc6a	T	A	10: 51,491,485 (GRCm39)	M755L	probably damaging	Het
H1f8	G	T	6: 115,924,729 (GRCm39)	K78N	probably damaging	Het
Lama1	A	T	17: 68,089,051 (GRCm39)	D1574V	possibly damaging	Het
Lama3	T	A	18: 12,537,160 (GRCm39)	H268Q	probably damaging	Het
Lmntd1	T	C	6: 145,363,202 (GRCm39)	D107G	probably damaging	Het
Lrriq1	A	G	10: 102,904,792 (GRCm39)	V1614A	probably damaging	Het
Mmp12	A	G	9: 7,350,152 (GRCm39)		probably benign	Het
Mre11a	A	G	9: 14,742,269 (GRCm39)		probably benign	Het
Mtrf1l	T	C	10: 5,765,553 (GRCm39)		silent	Het
Oaz2	A	G	9: 65,595,084 (GRCm39)	E61G	probably damaging	Het
Parp3	A	T	9: 106,348,600 (GRCm39)	D473E	possibly damaging	Het
Pkhd1l1	A	T	15: 44,437,203 (GRCm39)	T3493S	possibly damaging	Het
Ppp3cb	A	G	14: 20,581,820 (GRCm39)	V65A	possibly damaging	Het
Rheb	A	T	5: 25,022,832 (GRCm39)		probably benign	Het
Ros1	G	A	10: 51,977,899 (GRCm39)	T1449M	probably damaging	Het
Scn4a	C	G	11: 106,211,682 (GRCm39)	R1445P	probably damaging	Het
Sema3d	T	A	5: 12,634,920 (GRCm39)	M662K	probably benign	Het
Skp2	A	G	15: 9,125,178 (GRCm39)	F134L	probably benign	Het
Slc6a12	T	C	6: 121,337,378 (GRCm39)		probably benign	Het
Slc8a3	T	C	12: 81,362,039 (GRCm39)	Y260C	probably damaging	Het
Spin1	T	A	13: 51,304,454 (GRCm39)		probably benign	Het
Stx2	A	G	5: 129,076,572 (GRCm39)		probably null	Het
Sycp2	A	T	2: 178,006,504 (GRCm39)	V863D	probably damaging	Het
Tgfb3	T	A	12: 86,116,658 (GRCm39)	I127F	possibly damaging	Het
Tgif1	T	G	17: 71,157,879 (GRCm39)	K2Q	probably damaging	Het
Trmt2a	A	T	16: 18,068,707 (GRCm39)	E234D	probably damaging	Het
Trps1	A	T	15: 50,628,921 (GRCm39)	S696T	probably benign	Het
Ucp1	A	G	8: 84,020,857 (GRCm39)	E191G	probably damaging	Het
Usp48	C	A	4: 137,341,114 (GRCm39)	D371E	probably damaging	Het
Usp54	A	T	14: 20,623,823 (GRCm39)		probably benign	Het

Other mutations in Pear1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00326:Pear1	APN	3	87,659,423 (GRCm39)	missense	possibly damaging	0.65
IGL01810:Pear1	APN	3	87,659,608 (GRCm39)	missense	probably damaging	0.98
IGL02269:Pear1	APN	3	87,663,571 (GRCm39)	missense	probably damaging	1.00
IGL02635:Pear1	APN	3	87,657,453 (GRCm39)	makesense	probably null
R0040:Pear1	UTSW	3	87,661,665 (GRCm39)	missense	probably damaging	0.99
R0040:Pear1	UTSW	3	87,661,665 (GRCm39)	missense	probably damaging	0.99
R0050:Pear1	UTSW	3	87,663,294 (GRCm39)	nonsense	probably null
R0090:Pear1	UTSW	3	87,661,649 (GRCm39)	missense	possibly damaging	0.82
R0547:Pear1	UTSW	3	87,696,107 (GRCm39)	splice site	probably null
R1024:Pear1	UTSW	3	87,667,606 (GRCm39)	unclassified	probably benign
R1612:Pear1	UTSW	3	87,659,160 (GRCm39)	critical splice donor site	probably null
R1637:Pear1	UTSW	3	87,664,060 (GRCm39)	missense	probably damaging	0.97
R1772:Pear1	UTSW	3	87,661,799 (GRCm39)	unclassified	probably benign
R1888:Pear1	UTSW	3	87,717,882 (GRCm39)	splice site	probably benign
R2129:Pear1	UTSW	3	87,665,666 (GRCm39)	nonsense	probably null
R2255:Pear1	UTSW	3	87,659,493 (GRCm39)	missense	probably damaging	1.00
R3551:Pear1	UTSW	3	87,665,439 (GRCm39)	missense	probably benign
R3855:Pear1	UTSW	3	87,659,228 (GRCm39)	missense	possibly damaging	0.94
R4021:Pear1	UTSW	3	87,663,529 (GRCm39)	missense	possibly damaging	0.89
R4546:Pear1	UTSW	3	87,661,968 (GRCm39)	missense	probably damaging	1.00
R5364:Pear1	UTSW	3	87,665,668 (GRCm39)	missense	probably damaging	1.00
R5447:Pear1	UTSW	3	87,666,449 (GRCm39)	missense	probably damaging	1.00
R5504:Pear1	UTSW	3	87,660,002 (GRCm39)	splice site	probably benign
R6026:Pear1	UTSW	3	87,664,220 (GRCm39)	missense	probably damaging	1.00
R6061:Pear1	UTSW	3	87,663,238 (GRCm39)	missense	probably benign	0.02
R6155:Pear1	UTSW	3	87,666,875 (GRCm39)	missense	probably damaging	0.97
R6175:Pear1	UTSW	3	87,659,440 (GRCm39)	missense	possibly damaging	0.93
R6339:Pear1	UTSW	3	87,659,827 (GRCm39)	missense	probably damaging	1.00
R6385:Pear1	UTSW	3	87,661,506 (GRCm39)	missense	probably benign	0.00
R6715:Pear1	UTSW	3	87,666,424 (GRCm39)	missense	probably damaging	1.00
R6929:Pear1	UTSW	3	87,666,872 (GRCm39)	nonsense	probably null
R7088:Pear1	UTSW	3	87,661,945 (GRCm39)	missense	possibly damaging	0.80
R7097:Pear1	UTSW	3	87,658,752 (GRCm39)	missense	probably benign	0.00
R7229:Pear1	UTSW	3	87,657,596 (GRCm39)	missense	probably benign	0.00
R7334:Pear1	UTSW	3	87,657,532 (GRCm39)	missense	probably damaging	1.00
R7526:Pear1	UTSW	3	87,659,875 (GRCm39)	missense	probably damaging	0.99
R7872:Pear1	UTSW	3	87,659,522 (GRCm39)	missense	probably benign
R8925:Pear1	UTSW	3	87,661,890 (GRCm39)	missense	probably damaging	0.99
R8927:Pear1	UTSW	3	87,661,890 (GRCm39)	missense	probably damaging	0.99
R9014:Pear1	UTSW	3	87,658,479 (GRCm39)	missense	probably benign
R9405:Pear1	UTSW	3	87,659,890 (GRCm39)	missense	probably damaging	1.00
R9455:Pear1	UTSW	3	87,666,488 (GRCm39)	missense	possibly damaging	0.96
R9593:Pear1	UTSW	3	87,658,480 (GRCm39)	missense	probably benign	0.04
R9637:Pear1	UTSW	3	87,666,412 (GRCm39)	missense	probably benign	0.23
X0063:Pear1	UTSW	3	87,661,379 (GRCm39)	missense	probably damaging	1.00
Z1177:Pear1	UTSW	3	87,658,647 (GRCm39)	missense	possibly damaging	0.68

Protein Function and Prediction

Platelet endothelial aggregation receptor 1 (Pear1) is a type 1 membrane protein of the multiple epidermal growth factor (EGF)-like domain family that signals upon the formation of platelet-platelet contact (1-3). During platelet aggregation, PEAR1 is phosphorylated and recruits p85 PI3K, subsequently leading to the persistant activation of PI3K and Akt and the amplification of αIIbβ3 activation (3). Amplification of αIIbβ3 activation results in the stabilization of platelet aggregates (3). Pear1 also function in apoptotic neuron clearance in the embryonic dorsal root ganglia via an engulfment-dependent activity (4). SNPs in PEAR1 are linked to increased or decreased platelet responses to various agonists (2;5-7).

Expression/Localization

Pear1 is most highly expressed in platelets and endothelial cells followed by megakaryocytes, osteoblasts, coronary smooth muscle cells, and erythroid cells (1). Pear1 is also expressed in satellite glial cell precursors (4). In human tissues, PEAR1 expression was detected in heart, kidney, skeletal muscle, pancreas, ovary, breast, lung, brain cortex, hypothalamus, spinal cord, and dorsal root ganglion; expression was not detected in liver, small intestine, and colon (1).

References

1. Nanda, N., Bao, M., Lin, H., Clauser, K., Komuves, L., Quertermous, T., Conley, P. B., Phillips, D. R., and Hart, M. J. (2005) Platelet Endothelial Aggregation Receptor 1 (PEAR1), a Novel Epidermal Growth Factor Repeat-Containing Transmembrane Receptor, Participates in Platelet Contact-Induced Activation. J Biol Chem. 280, 24680-24689.

2. Faraday, N., Yanek, L. R., Yang, X. P., Mathias, R., Herrera-Galeano, J. E., Suktitipat, B., Qayyum, R., Johnson, A. D., Chen, M. H., Tofler, G. H., Ruczinski, I., Friedman, A. D., Gylfason, A., Thorsteinsdottir, U., Bray, P. F., O'Donnell, C. J., Becker, D. M., and Becker, L. C. (2011) Identification of a Specific Intronic PEAR1 Gene Variant Associated with Greater Platelet Aggregability and Protein Expression. Blood. 118, 3367-3375.

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Posted On

2013-01-08

Science Writer

Anne Murray