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Original article
Proficiency of 38 HID-INDELS in kinship analysis and forensic parameters in a Mexican population
Eficiencia de 38 HID-INDELS en análisis de parentesco y parámetros forenses en una población mexicana
J.A. Aguilar-Velázqueza, E. Rojas-Pradoa, G. Martínez-Cortésa, A.F. Favela-Mendozaa, A. González-Martinb, H. Rangel-Villalobosa,
Corresponding author
hrangel13@hotmail.com
hector.rangel@academicos.udg.mx

Corresponding author at: Instituto de Investigación en Genética Molecular, Universidad de Guadalajara, Centro Universitario de la Ciénega (CUCiénega-UdeG), Av. Universidad #1115, Col. Paso Blanco, CP 47810, Ocotlán, Jalisco, Mexico.
a Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara (CUCiénega-UdeG), Ocotlán, Jalisco, Mexico
b Departamento de Biodiversidad, Ecología y Evolución, Universidad Complutense de Madrid, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">During the last decades&#44; autosomal Short tandem repeat &#40;STR&#41; loci have constituted the markers of choice for Human identification &#40;HID&#41; purposes&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> However&#44; poor-quality samples commonly found in forensic casework generate partial STR profiles that complicate reaching conclusions &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span> ancient or degraded DNA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> Similarly&#44; the relatively high mutation rate of STRs generates sporadic inconsistencies in kinship analysis&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> Although Single nucleotide polymorphisms &#40;SNPs&#41; have been implemented for HID purposes&#44; they require instruments non-available in the majority of forensic genetic labs and&#47;or involve no conventional methodologies&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> Conversely&#44; Insertion&#8211;Deletion length polymorphisms &#40;INDELs&#41; have been easily incorporated in forensic casework by means of short amplicon multiplexes followed by traditional capillary electrophoresis&#46;<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5&#8211;7</span></a> Particularly&#44; both SNPs and INDELs biallelic loci have been useful for analysis of highly degraded skeletal remains&#44;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> and to deal with occasional STR mutations in paternity testing due to their low mutation rate&#46;<a class="elsevierStyleCrossRefs" href="#bb0045"><span class="elsevierStyleSup">9&#8211;11</span></a> Consequently&#44; genetic systems based on HID-INDELs have been studied in worldwide populations to estimate allele frequencies and <span class="elsevierStyleItalic">a priori</span> forensic parameters&#44; such as heterozygosity&#44; power of discrimination &#40;PD&#41;&#44; power of exclusion &#40;PE&#41;&#44; and typical paternity index &#40;IP&#41;&#44; principally&#46;<a class="elsevierStyleCrossRefs" href="#bb0060"><span class="elsevierStyleSup">12&#8211;14</span></a> However&#44; informativity weaknesses due to their biallelic condition have been described for kinship analysis&#44; particularly in motherless duo-cases&#44;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> and when the alleged father is a close relative of the real one&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Interestingly&#44; some parameters <span class="elsevierStyleItalic">a posteriori</span> such as the Paternity index &#40;PI&#41;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> have demonstrated to be useful to evaluate the actual contribution of genetic markers in conventional kinship analyses&#44;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> which would be worthy to avoid wasting work&#44; resources&#44; and &#8211;finally&#8211; disappointments&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">For this reason&#44; we analyzed the 38-plex INDEL system in 25 Mexican families from the Jalisco state&#44; including the father &#40;F&#41;&#44; mother &#40;M&#41;&#44; and daughter &#40;D&#41; with previously established kinship based on 22 autosomal STRs&#46; The aims of this study were the following&#58; 1&#41; to evaluate the proficiency provided by the 38plex INDEL system to confirm kinship &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span> PI&#41; in these families fitted as standard trio and duo paternity cases &#40;motherless and fatherless&#41;&#59; 2&#41; to update the forensic parameters of the studied Mexican population using INDEL genotypes from unrelated individuals and previously reported&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Materials and methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Studied sample</span><p id="p0015" class="elsevierStylePara elsevierViewall">A total of 75 volunteers from 25 Mexican families from the Jalisco state &#40;West&#44; Mexico&#41; were analyzed&#46; Genetic relationships were previously confirmed with 22 autosomal STRs by the Powerplex Fusion kit &#40;Powerplex Fusion System&#44; Promega Corp&#46;&#41; displaying a PI &#8805;<span class="elsevierStyleHsp" style=""></span>1&#46;46E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>12&#46; These 25 families also constitute 25 standard paternity cases &#40;trio&#41;&#44; with 50 unrelated persons &#40;fathers plus mothers&#41;&#44; plus 25 individuals corresponding to the offspring&#46; All individuals of each family signed a written informed consent agreeing to the ethical guidelines of the Helsinki Declaration&#46; This study was approved by the local Ethical Research Committee of the Research Institute in Molecular Genetics&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Laboratory analysis</span><p id="p0020" class="elsevierStylePara elsevierViewall">Genomic DNA was collected from bloodstain samples impregnated on FTA papers&#46; Bloodstain punches of 1&#46;2&#8239;mm washed with FTA Purification Reagent &#40;Whatman&#8482;&#41; and DNAsa-free water&#44; were directly used as DNA samples for further analysis&#46; Genotypes for the 38 autosomal INDELS were obtained using the PCR multiplex protocol previously described for this genetic system&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> Separation and detection of PCR products were performed with an ABI Prism 3130 Genetic Analyzer&#44; and using the GeneMapper v3&#46;2 software &#40;Applied Biosystems&#44; Foster City&#44; CA&#41;&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Data analysis</span><p id="p0025" class="elsevierStylePara elsevierViewall">Firstly&#44; for each Mexican family&#44; the paternity index &#40;PI&#41; was estimated by INDEL locus and combined PI for each standard trio case &#40;n&#8239;&#61;&#8239;25&#41;&#46; Moreover&#44; PI&#39;s were computed omitting one parent&#44; adapting data as motherless and fatherless paternity duo-cases &#40;n&#8239;&#61;&#8239;50&#41;&#46; When the probability of paternity &#40;W&#41; was estimated&#44; a flat <span class="elsevierStyleItalic">a priori</span> probability of 0&#46;5 was taken into account for both paternity hypotheses&#58; kinship and unrelated&#46; With the INDEL genotypes of unrelated individuals&#44; specifically fathers and mothers &#40;n&#8239;&#61;&#8239;50&#41;&#44; plus those previously reported &#40;n&#8239;&#61;&#8239;62&#41;&#44;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> we were able to updated the forensic parameters of the Jalisco state &#40;n&#8239;&#61;&#8239;112&#41;&#46; The updated allele frequencies were used to compute the PI values with PATPCR&#44; a free Excel spreadsheet designed by JA Luque &#40;Barcelona&#44; Spain&#44; 2002&#41;&#46; Although individuals of the paternity cases are included in the updated Mexican population database&#44; a minimal effect is expected given the biallelic condition of INDEL markers&#46; The Microsoft Excel spreadsheet Powerstats<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> was used to compute the following <span class="elsevierStyleItalic">a priori</span> forensic parameters&#58; allele frequencies&#44; observed heterozygosity &#40;Ho&#41;&#44; expected heterozygosity &#40;He&#41;&#44; power of discrimination &#40;PD&#41;&#44; typical paternity index &#40;TPI&#41;&#44; and polymorphic information content &#40;PIC&#41;&#46; However&#44; the power of exclusion &#40;PE&#41; was computed with an specific formula for biallelic loci &#91;PE&#8239;&#61;&#8239;pq &#40;1-pq&#41;&#93;&#46; Finally&#44; exact tests to assess Hardy&#8211;Weinberg expectations &#40;HWE&#41; and linkage disequilibrium &#40;LD&#41; between pairs of loci were performed using the GDA software&#46;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a></p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Results and discussions</span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Kinship informativity of the 38plex INDEL system</span><p id="p0030" class="elsevierStylePara elsevierViewall">The complete 38-plex INDEL genotypes of the Mexican families are available in the Supplementary table S1&#46; As expected by the low mutation rate of the INDEL loci&#44;<a class="elsevierStyleCrossRefs" href="#bb0045"><span class="elsevierStyleSup">9&#8211;11</span></a> any exclusion parent-daughter was observed&#44; and PIs were estimated to evaluate the performance of the 38-plex INDEL system for kinship analysis &#40;Supplementary table S2a and S2b&#41;&#46; In duo paternity cases&#44; the average PI values in fatherless &#40;32&#44;119&#41; and motherless cases &#40;40&#44;716&#41; were similar &#40;P&#8239;&#61;&#8239;0&#46;8579&#59; t-student test&#41;&#44; as could be expected&#46; However&#44; differences between PIs from trio and duo paternity cases were evident &#40;P&#8239;&#60;&#8239;0&#46;0001&#59; t-student test&#41;&#44; as shown in <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#46; Concerning the informativity by INDEL locus&#44; R09 was the most informative locus in trio paternity cases with the largest range &#40;average PI&#8239;&#61;&#8239;2&#46;302&#59; range&#8239;&#61;&#8239;0&#46;5803&#8211;7&#46;2254&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#44; which is associated with the extreme allele frequencies of R09 &#8211;closer to zero and one&#8211; that result in the largest and smallest PI values&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Based on duo paternity cases&#44; R06 was the most informative INDEL locus &#40;average PI&#8239;&#61;&#8239;1&#46;5067&#41;&#46; Conversely&#44; although R03 displayed the minimum average PI &#40;1&#46;1407&#41;&#44; R09 showed the smallest PI value &#40;0&#46;5803&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0035" class="elsevierStylePara elsevierViewall">The generally accepted minimum standard PI for inclusion of paternity is &#8805;<span class="elsevierStyleHsp" style=""></span>100&#44;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> but presently the majority of the labs attached to the English-Speaking Group of the International Society of Forensic Genetics &#40;ESG-ISFG&#41; require a PI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10&#44;000&#44;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> which is probably required in most worldwide paternity testing labs&#46; These PIs correspond to probabilities of paternity &#40;W&#41; of 99 and 99&#46;99&#37;&#44; respectively&#44; assuming a flat <span class="elsevierStyleItalic">a priori</span> probability &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;5&#41;&#46; From the studied Mexican families in standard paternity trio-cases&#44; the 38-plex INDEL system displayed an average combined PI&#8239;&#61;&#8239;1&#46;63E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>05 &#40;range&#58; 1&#46;09E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>02 to 1&#46;29E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>06&#41;&#46; However&#44; 32&#37; &#40;8&#47;25&#41; of these PI values are below the limit required in most of the paternity laboratories &#40;PI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10&#44;000&#41;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> &#40;Supplementary table S2a&#41;&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">On the other hand&#44; the Mexican families adapted as paternity duo-cases showed an average combined PI&#8239;&#61;&#8239;3&#46;64E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>04 &#40;range&#58; 5&#46;98 to 9&#46;55E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>05&#41;&#44; but only 12&#37; of these values &#40;6&#47;50&#41; reached the required limit to establish paternity &#40;PI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#44;000&#41; &#40;Supplementary table S2b&#41;&#46; Even 14&#37; &#40;7&#47;50&#41; of these paternity duo-cases neither reached the minimum standard for inclusion of paternity &#40;PI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100&#41; <a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> &#40;Supplementary table S2b&#41;&#46; In brief&#44; the estimated performance of the 38-plex INDEL system to establish confident kinship from real standard trio and duo cases was only 68&#37; and 12&#37;&#44; respectively&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">These results highlight the role of the 38-plex system as a complementary genetic system to establish paternity&#46; This is in agreement with the limitations described for biallelic markers to solve duo paternity cases&#44;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> and when the alleged father &#40;AF&#41; is a close relative of the real father&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> For instance&#44; to discard the four-step mutation hypothesis between the AF and child in the autosomal STR D22S1045&#44; concerning the brother of the AF paternity hypothesis&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> In this study&#44; although the AF paternity hypothesis was favored with the 81 HID markers analyzed &#40;LR&#8239;&#61;&#8239;13&#46;4&#59; W&#8239;&#61;&#8239;93&#46;1&#37;&#41;&#44; 58 INDELs &#8211;by themselves&#8211; were not conclusive enough &#40;LR&#8239;&#61;&#8239;110&#46;3&#44; W&#8239;&#61;&#8239;99&#46;1&#37;&#41;&#46; Conversely&#44; the 38-plex INDEL system has contributed successfully to solve complex paternity cases&#44; such as supporting the hypothesis of maternal uniparental disomy of chromosome 2&#44; despite the exclusions presence&#46;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">a priori</span> forensic parameter for standard paternity cases&#44; known as Typical paternity index &#40;TPI&#41;&#44;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> was compared with its corresponding <span class="elsevierStyleItalic">a posteriori</span> analog based on the Mexican paternity cases studied herein &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#41;&#46; By INDEL locus&#44; the average TPI was minor than one &#40;PI&#8239;&#61;&#8239;0&#46;94&#59; range&#58; 0&#46;6222 to 1&#46;2727&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; This finding means that &#8211;theoretically&#8211; each INDEL marker commonly does not contribute statistically to confirm true paternities&#44; despite the observed parent&#8211;child match &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>A&#41;&#46; Conversely&#44; the average PI estimated herein was larger than one&#44; for both standard trio &#40;PI&#8239;&#61;&#8239;1&#46;4189&#59; range&#8239;&#61;&#8239;1&#46;2009&#8211;2&#46;3055&#41; and duo paternity cases &#40;PI&#8239;&#61;&#8239;1&#46;2725&#59; range&#8239;&#61;&#8239;1&#46;1407&#8211;1&#46;5067&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Consequently&#44; INDELs contribute &#8211;modestly&#8211; to establish previously verified kinship &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>A&#41;&#46; Interestingly&#44; the product of the average TPI from the 38 INDELs did not support the paternity hypothesis &#40;TPI&#8239;&#61;&#8239;0&#46;0688&#59; W&#8239;&#61;&#8239;6&#46;43&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#59; <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>B&#44; C&#41;&#46; On the other hand&#44; the product of the average PI from the 38 INDELs helped to verify the kinship in both trios &#40;PI&#8239;&#61;&#8239;4&#46;76E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>05&#59; W&#8239;&#61;&#8239;99&#46;99979&#37;&#41; and duo paternity cases &#40;PI&#8239;&#61;&#8239;8&#46;58E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03&#59; W&#8239;&#61;&#8239;99&#46;98833&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>B&#44; C&#41;&#46; In brief&#44; these results show that TPI undervalues the informativity provided by HID-INDELs &#8211;and consequently SNPs&#8211; to verify kinship&#59; therefore&#44; this <span class="elsevierStyleItalic">a priori</span> forensic parameter should be redesigned according to the low polymorphism of these biallelic markers&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Updating forensic parameters in a Mexican population</span><p id="p0055" class="elsevierStylePara elsevierViewall">The INDEL genotypes from unrelated individuals studied herein &#40;father and mother&#41;&#44; were combined to the corresponding previously reported Mexican population dataset &#40;Supplementary table S3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> Therefore&#44; we updated the allele frequencies and forensic parameters of the 38 HID-Indels in the Jalisco state &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#44; increasing the sample size from 62 to 112 individuals&#44; improving the parameter&#39;s confidence&#46; The average heterozygosities observed &#40;Ho&#41; and expected &#40;He&#41; in these 38 INDELs were 0&#46;4505 and 0&#46;4461&#44; respectively&#46; By INDEL&#44; the observed heterozygosity &#40;Ho&#41; ranged from 0&#46;1875 to 0&#46;5804&#44; whereas the expected heterozygosity &#40;He&#41; ranged from 0&#46;2385 to 0&#46;500&#44; for the INDEL loci R09 and G02&#44; respectively&#46; Particularly&#44; R09 showed the lowest of PD&#44; PE&#44; TPI&#44; and PIC values &#40;37&#46;3&#37;&#44; 10&#46;5&#37;&#44; 0&#46;6154 and 21&#37;&#44; respectively&#41;&#46; Conversely&#44; G07 showed the highest PD &#40;65&#37;&#41;&#44; and G02 showed the highest PE&#44; PIC&#44; and TPI values &#40;18&#46;75&#37;&#44; 37&#46;5&#37;&#44; and 1&#46;19&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46; Although the combined PD for the 38 INDELS in the Mexican population of Jalisco is large &#40;99&#46;9999999999997&#37;&#41;&#44; the combined PE is relatively low &#40;99&#46;93&#37;&#41; regarding what is provided by conventional autosomal STR kits in the same Mexican population&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a></p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0060" class="elsevierStylePara elsevierViewall">For all the 38 INDELs&#44; the genotype distributions were in agreement with Hardy&#8211;Weinberg equilibrium &#40;HWE&#41; expectations in the Jalisco state population&#44; excepting G08 &#40;p&#8239;&#61;&#8239;0&#46;0475&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; However&#44; after applying Bonferroni&#39;s correction for multiple tests &#40;0&#46;05&#47;38&#8239;&#61;&#8239;0&#46;0013&#41;&#44; all INDEL markers agree with the HWE expectations&#46; Similarly&#44; LD exact tests discarded allelic association between all pairwise combinations for the 38 INDEL loci &#40;data not shown&#41;&#46; In brief&#44; these results &#40;HWE and LD tests&#41; validate the confident use of the binomial expansion of &#40;p&#8239;&#43;&#8239;q&#41;2 and the product rule&#44; respectively&#44; to calculate the random matching probability &#40;RMP&#41; of DNA profiles based on HID-INDEL in forensic casework and kinship analyses&#46;</p></span></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Conclusions</span><p id="p0065" class="elsevierStylePara elsevierViewall">Based on the analysis of 38 HID-INDELs in 25 Mexican families&#44; we evaluated the proficiency provided by the genetic system to verify paternity through the PI&#46; Important limitations arose when one parent was omitted from the kinship test&#44; emphasizing the complementary value of this HID system&#46; The comparison of PI&#44; <span class="elsevierStyleItalic">a posteriori</span> kinship parameter&#44; with the corresponding <span class="elsevierStyleItalic">a priori</span> parameter TPI&#44; suggest that this should be redesigned for biallelic loci&#46; Finally&#44; we updated forensic parameters for the populations where the families come from &#40;Jalisco state&#44; Mexico&#41;&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Introduction</span><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Insertion&#8211;deletions for human identification &#40;HID-INDELs&#41; allow solving peculiar forensic situations when autosomal STRs are insufficient&#46; Although limitations were predicted since the forensic implementation of biallelic markers&#44; formal evaluation of these restrictions is scarce&#46; Particularly&#44; to define the informativity provided by HID-INDELs in kinship analysis is useful to avoid wasting work&#44; resources&#44; and &#8211;finally&#8211; disappointments&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Material and methods</span><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">For this reason&#44; we analyzed the 38-plex HID-INDEL system in 25 Mexican families including father&#44; daughter&#44; and mother&#44; whose kinship was previously established with 22 autosomal STRs&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results and discussion</span><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">From genotypes of unrelated individuals&#44; we updated allele frequencies and forensic parameters of the Jalisco state &#40;West&#44; Mexico&#41;&#44; by increasing the population sample size from 62 to 112&#46; Among the forensic <span class="elsevierStyleItalic">a priori</span> parameters&#44; the Typical paternity index &#40;PI&#41; of the 38plex HID-INDEL system showed important differences regarding the PI and probability of paternity &#40;W&#41; estimated herein from real paternity cases&#44; generally undervaluing the observed informativity of these 38-plex HID-INDEL system&#46; Conversely&#44; the studied HID-INDEL loci offered confident kinship conclusions based on the paternity index &#40;PI &#8805;<span class="elsevierStyleHsp" style=""></span>10&#44;000&#41; and probability of paternity &#40;W&#8239;&#8805;&#8239;99&#46;99&#37;&#41; in 68&#37; of the standard trio cases &#40;18&#47;25&#41;&#44; and only 12&#37; of duo paternity cases &#40;6&#47;50&#41; &#40;motherless and fatherless&#41;&#46; In fact&#44; 14&#37; of duo paternity cases &#40;7&#47;50&#41; did not reach minimum requirements to stablish paternity &#40;IP&#8239;&#60;&#8239;100&#59; W&#8239;&#60;&#8239;99&#37;&#41;&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusions</span><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">We updated a Mexican population database for 38 HID-INDEL loci&#44; and we described their proficiency from real paternity cases&#44; detailing some limitations non-previously specified&#46;</p></span>"
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        "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Introducci&#243;n</span><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Las inserciones-deleciones para identificaci&#243;n humana &#40;HID-INDEL&#41;&#44; permiten resolver situaciones forenses peculiares cuando los STR autos&#243;micos son insuficientes&#46; Aunque se predijeron sus limitaciones desde la implementaci&#243;n forense de marcadores bial&#233;licos&#44; la evaluaci&#243;n formal de estas restricciones es escasa&#46; Particularmente es &#250;til definir su informatividad en el an&#225;lisis de parentesco&#44; para evitar desperdiciar trabajo&#44; recursos y &#8211;finalmente&#8211; decepciones&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Material y M&#233;todos</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Por este motivo&#44; analizamos el sistema de 38plex HID-INDELs en 25 familias mexicanas entre padre&#44; hija y madre&#44; cuyo parentesco se estableci&#243; previamente con 22 STR autos&#243;micos&#46; A partir de los individuos no emparentados&#44; actualizamos las frecuencias al&#233;licas y los par&#225;metros forenses del estado de Jalisco &#40;Oeste&#44; M&#233;xico&#41;&#44; aumentando el tama&#241;o de la muestra poblacional de 62 a 112&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados y discusi&#243;n</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Entre los par&#225;metros forenses <span class="elsevierStyleItalic">a priori</span>&#44; el &#237;ndice de paternidad t&#237;pico &#40;IPT&#41; del sistema 38plex HID-INDEL mostr&#243; diferencias importantes con respecto al IP y la probabilidad de paternidad &#40;W&#41; derivados de casos reales de paternidad&#44; generalmente subestimando la informatividad observada de ese sistema&#46; Sin embargo&#44; los 38 HID-INDELs ofrecieron conclusiones de parentesco confiables basadas en el &#237;ndice de paternidad &#40;IP&#8239;&#8805;&#8239;10&#44;000&#41; y la probabilidad de paternidad &#40;W&#8239;&#8805;&#8239;99&#44;99&#37;&#41; s&#243;lo en el 68&#37; de los casos tr&#237;os est&#225;ndar &#40;18&#47;25&#41;&#44; y el 12&#37; de casos de paternidad d&#250;o &#40;6&#47;50&#41; &#40;sin madre y sin padre&#41;&#46; De hecho&#44; el 14&#37; de los casos de paternidad d&#250;o &#40;7&#47;50&#41; no alcanz&#243; los requisitos m&#237;nimos para establecer la paternidad &#40;IP &#60;<span class="elsevierStyleHsp" style=""></span>100&#59; W&#8239;&#60;&#8239;99&#37;&#41;&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusiones</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">En este trabajo actualizamos una base de datos de poblaci&#243;n mexicana para 38 HID-INDELs y describimos su eficiencia en casos reales de paternidad&#44; detallando algunas limitaciones no especificadas previamente&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "as0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "as0030"
            "titulo" => "Material y M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "as0035"
            "titulo" => "Resultados y discusi&#243;n"
          ]
          3 => array:2 [
            "identificador" => "as0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="p0080" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="ec0005"></elsevierMultimedia><elsevierMultimedia ident="ec0010"></elsevierMultimedia><elsevierMultimedia ident="ec0015"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "s0050"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "f0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1980
            "Ancho" => 1299
            "Tamanyo" => 125783
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0005"
            "detalle" => "Fig&#46; "
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        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Comparison of kinship results form typical paternity index &#40;TPI&#41; <span class="elsevierStyleItalic">versus</span> those from standard trio an duo paternity cases for the 38 HID-INDELs<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>&#58; a&#41; Average PI of individual markers&#59; b&#41; Combined from average PI of markes&#59; c&#41; Probability of paternity &#40;W&#41; from values described in incise b&#41;&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 1"
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        "mostrarFloat" => true
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          0 => array:3 [
            "identificador" => "al0010"
            "detalle" => "Table "
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;5601</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;2445</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">rs2308171</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6154&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">2&#46;0355</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;4297</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">R10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">rs35605984</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;3439</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;1613</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Average</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;9260&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;4189</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46;2725</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">maximum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;5067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">minimum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;6222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1407&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Combined PI</span><a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup"><span class="elsevierStyleBold">&#163;</span></span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">3&#46;91E-02</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#46;76E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>05</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">8&#46;58E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>03</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paternity probability &#40;W&#41;<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">&#8225;</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;376&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;9999979&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9998833&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">MID</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">PD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">IPT</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">PIC</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">p-value</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">B01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MID-2719&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs34541393&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;4732&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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ISSN: 24454249
Original language: English
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