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Not for further distribution unless allowed by the License or with the express written permission of Cambridge University Press.
https://doi.org/10.1017/S0317167100006776
https://doi.org/10.1017/S0317167100006776 Published online by Cambridge University Press
2022-04-12T19:44:34+00:00
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(\()Tj
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[(A)37(TP13A2)]TJ
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[(1p36\); P)92(ARK10 (1p);)]TJ
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ET
Q
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(LRRK2)Tj
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0 Tc
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[(has been shown to have dif)18(fering)]TJ
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[(mutations of varying frequency among dif)18(ferent ethnic groups.)]TJ
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0.141 Tw
[(The high frequency of the G2019S mutation in North )55(African)]TJ
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0.03 Tw
[(Arabs (30%) and )55(Ashkenazi Jewish PD subjects (18%) supports)]TJ
T*
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0.493 Tw
(the presence of an ancient founder mutation in these)Tj
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0 Tw
(populations.)Tj
ET
Q
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ET
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[(A)-309(significant proportion of mutations in )]TJ
ET
Q
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BT
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(LRRK2)Tj
ET
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ET
Q
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(LRRK2)Tj
ET
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BT
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[(particularly mutations af)18(fecting amino acids 1441 and 2019)]TJ
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ET
Q
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(4)Tj
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(-7)Tj
ET
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(We)Tj
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(screened these two exons in a sample of French Canadian (FC))Tj
T*
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ET
Q
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BT
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(LRRK2)Tj
ET
Q
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/GS1 gs
q
BT
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(were associated with PD in the FC founder population.)Tj
ET
Q
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/GS1 gs
q
BT
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(M)Tj
ET
Q
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q
BT
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(ETHODS)Tj
ET
Q
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q
BT
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(Cases were recruited through a designated movement)Tj
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0 Tc
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0 Tc
0.079 Tw
(neurologist specialized in movement disorders and had to meet)Tj
T*
0.035 Tw
[(the )18(W)80(ard and Gibb criteria for PD.)]TJ
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
(8)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
0.035 Tw
[(Additionally)65(, they had to be)]TJ
-14.57992 -1.15789 TD
0 Tw
(dopa-responsive. )Tj
7.31332 0 TD
(A)Tj
1.23251 0 TD
0.316 Tw
(detailed standardized clinical assessment)Tj
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-0.008 Tw
[(form was completed for each subject. )55(All cases signed a consent)]TJ
T*
0.058 Tw
(form approved by the ethics committee of the CHAUQ prior to)Tj
0 -1.15789 TD
0.04 Tw
[(being enrolled in the study)65(. )55(A)-235(structured questionnaire was used)]TJ
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0.051 Tw
(during the interview to assess environmental, medical, lifestyle,)Tj
T*
0.002 Tw
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0 -1.15789 TD
0.233 Tw
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0 -1.1579 TD
0.025 Tw
(controls were collected from the same base population.)Tj
29.59327 42.10526 TD
0.374 Tw
(Upon receipt of informed consent, blood samples were)Tj
-1.26316 -1.15789 TD
0.154 Tw
[(obtained from 125 af)18(fected individuals and 95 controls. DNA)]TJ
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0.368 Tw
(was extracted from peripheral blood by standard methods.)Tj
0 -1.15789 TD
-0.016 Tw
(Exons 31 and 41 of )Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F3 1 Tf
9.5 0 0 9.5 384.6469 682.5035 Tm
0 0 0 1 k
(LRRK2)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
9.5 0 0 9.5 414.8427 682.5035 Tm
0 0 0 1 k
-0.016 Tw
(were amplified by PCR with intronic)Tj
-11.1245 -1.15789 TD
0.057 Tw
[(primers in all af)18(fected individuals and directly sequenced on an)]TJ
0 -1.1579 TD
0.02 Tc
0.574 Tw
[(ABI 3700 sequencer)40(, according to the manufacturer)-3755(s)]TJ
0 -1.15789 TD
0 Tc
0.093 Tw
[(recommended protocol \(Applied Biosystems, Foster City)65(, CA\).)]TJ
T*
0.113 Tw
(Six single nucleotide polymorphisms (SNPs) were typed in all)Tj
0 -1.1579 TD
0.108 Tw
[(af)17(fected individuals and non-disease controls. )18(The SNPs were)]TJ
0 -1.15789 TD
0.016 Tw
[(selected using )55(Applied Biosystems SNPbrowser\252)-266(Software and)]TJ
T*
0.015 Tw
(the HapMap project Linkage Disequilibrium (LD) map included)Tj
0 -1.1579 TD
0.002 Tw
[(within the software. )55(At least 3 SNPs per Linkage Disequilibrium)]TJ
0 -1.15789 TD
0.071 Tw
(Unit (LDU) were chosen complete coverage of )Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F3 1 Tf
9.5 0 0 9.5 495.0426 583.5035 Tm
0 0 0 1 k
(LRRK2)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
-0.0001 Tc
(.)Tj
0.57043 0 Td
0 Tc
0.071 Tw
(Due to)Tj
-23.08161 -1.15789 TD
0.107 Tw
[(the high LD of this locus, only 6 SNPs were suf)18(ficient for the)]TJ
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-0.027 Tw
[(purpose of this association study \(T)70(able 1\). )55(Associations between)]TJ
0 -1.15789 TD
0.281 Tw
(unrelated cases and matched controls were analyzed by the)Tj
T*
0.014 Tc
0.361 Tw
(program COCAPHASE included in the software package)Tj
0 -1.1579 TD
0 Tc
0 Tw
(UNPHASED.)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
(9)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
0.011 Tw
(This software is based on likelihood ratio tests in)Tj
-6.15512 -1.15789 TD
0.0082 Tc
(a)Tj
1.07705 0 Td
0.008 Tc
0.367 Tw
(log-linear model. Single marker analysis and haplotype)Tj
-1.07705 -1.15789 TD
0 Tc
0.212 Tw
(association tests were performed. Haplotype sliding windows)Tj
0 -1.1579 TD
0.025 Tw
[(containing from 2 to 6 SNPs were analyzed \(T)70(able 2\).)]TJ
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F1 1 Tf
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0 0 0 1 k
(R)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F1 1 Tf
7.125 0 0 7.125 316.0183 462.5035 Tm
0 0 0 1 k
0.001 Tc
[(ESUL)93(T)-1(S)]TJ
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
0.218 Tw
[(A)-413(summary of the clinical data can be found in )18(T)70(able 3.)]TJ
-1.26316 -1.1579 TD
0.003 Tc
0.372 Tw
(Sequencing analysis did not reveal any reported or novel)Tj
0 -1.15789 TD
0 Tc
0.101 Tw
(mutations in exons 31 and 41 of )Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F3 1 Tf
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0 0 0 1 k
(LRRK2)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
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0 0 0 1 k
-0.0001 Tc
(.)Tj
0.6007 0 Td
0 Tc
0.101 Tw
(Neither non-reported)Tj
-17.33294 -1.1579 TD
0.197 Tw
(synonymous coding SNPs nor non-synonymous coding SNPs)Tj
T*
-0.018 Tw
[(were found. )18(The G2019S mutation as well as mutations af)17(fecting)]TJ
0 -1.15789 TD
-0.025 Tw
(amino acid 1441 were absent in all 125 af)Tj
16.49786 0 TD
(fected individuals. )Tj
7.79336 0 TD
0 Tw
(The)Tj
-24.29122 -1.1579 TD
-0.03 Tw
[(case-control association study on 125 af)18(fected individuals and 95)]TJ
T*
0.085 Tw
(controls did not provide any positive signal that would suggest)Tj
0 -1.15789 TD
0.065 Tw
(the presence of a common variant of )Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F3 1 Tf
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0 0 0 1 k
(LRRK2)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
9.5 0 0 9.5 485.5647 359.5035 Tm
0 0 0 1 k
0.065 Tw
(in the FC founder)Tj
-18.56891 -1.1579 TD
0.124 Tw
[(population. )55(As shown in )18(T)70(able 2, single-marker and haplotype)]TJ
T*
0.025 Tw
[(analyses systematically gave non-significant P)-238(values.)]TJ
ET
0 0 0 0 k
39.696 726 516 30 re
f
Q
/GS2 gs
/GS1 gs
q
BT
/F0 1 Tf
9 0 0 9 39.696 749.8455 Tm
0 0 0 1 k
-0.0001 Tc
(THE)Tj
2.21865 0 Td
0 Tc
0.025 Tw
[(CANADIAN JOURNAL)-238(OF NEUROLOGICAL)-238(SCIENCES)]TJ
-2.21865 -80.04603 TD
(334)Tj
ET
Q
/GS2 gs
/GS1 gs
q
BT
/F1 1 Tf
9.5 0 0 9.5 40.024 231.6926 Tm
0 0 0 1 k
0.001 Tc
0.255 Tw
[(T)92(able 1: SNPs selected in the LRRK2 gene. CEU MAF:)]TJ
1.26316 -1.15789 TD
0.017 Tw
[(allele fr)19(equency determined in the HapMap pr)18(oject using)]TJ
T*
0.324 Tw
(60 CEPH Utah fr)Tj
8.3699 0.00001 TD
[(om Nor)1(thern and )19(W)54(estern Eur)18(ope. )]TJ
-8.3699 -1.15791 TD
0.264 Tw
(CEU LDU: Linkage disequilibrium units based on 60)Tj
0 -1.15789 TD
0.025 Tw
(CEPH Utah fr)Tj
6.19698 0.00001 TD
(om Nor)Tj
3.27354 0.00001 TD
[(thern and )19(W)54(estern Eur)18(ope.)]TJ
ET
1 w
0 0 0 1 K
39.024 68.9279 m
286.2 68.9279 l
S
39.024 245.254 m
286.2 245.254 l
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