Kamis, 17 Juli 2014



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P-166
Amplification of very small amounts of DNA in sub-µl volumes in routine:
A new platform for on-chip PCR


Wolfgang Mann, Ulrike Schön, Tanja Schmitt, Thomas Zacher, Kerstin Hagen Mann

ALOPEX GmbH, Fritz-Hornschuch-Str. 7, D-95326 Kulmbach, Germany

Amplification of small amounts of nucleic acids is a challenge for a number of questions in genetics and forensics. In terms of commercially available kits for typing DNA sensitivity of those products is given in amounts of pg / sample to be analysed with or without allelic drop outs (ADOs). A technical reason for generation ADOs is simply the fact that a sequence might be missing because of the nature of a DNA dilution series. Small numbers of molecules cannot be distributed homogenously into seperated reaction vessels. Approaches like the digital PCR try to circumvent this obstacle by analysing the total volume that was amplified and try to detect any reaction with at least one starting molecule in a very large number of amplification reactions.
We have adressed the challenge by introducing a new amplification platform (AmpliGrid) that is suitable for amplifying small amounts of nucleic acids on a glass chip. The advantage by using this new platform is the optical inspection of the biological sample via microscope (since it is a glass substrate) immediately before starting the amplification in a one µl reaction. It is no problem to determine e.g. the number of starting cells each reflecting one single genome equivalent. Now the challenge to amplify one, two or three copies of a single sequence is no longer dependent on dilution series as described above. Furthermore, the frequency of ADOs is proportional to amplification parameters and no longer the analysis of technical ADOs based on the fact that there was not any starting target copy of the sequence to be analysed.
Hundreds of single cell PCRs have been carried out and a systematic study on the ADO phaenomenon based on commercially availabe multiplex typing kits will be presented.


P-167
Detection of microchimerism using short tandem repeats in patients submitted to blood transfusion

Mardini AC1, Schumacher S1, Albarus MH1, Rodenbusch R1, Giugliani R1,2, Matte U1, Saraiva-Pereira ML1,3.
1Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
2Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
3Biochemistry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

DNA analysis is a common method to diagnose several genetic and infectious diseases. Identification of microsatellite (short tandem repeats – STR) marker sets is normally used in many laboratories for human identification, helping in solving paternity as well as forensic cases. All of these studies use polymerase chain reaction (PCR) to amplify DNA extracted from peripherally drawn blood. As PCR is highly sensitive procedure, capable of amplifying even 1 molecule of DNA, sources of contamination have to be eliminated. However, transfusion might be a source of DNA contamination in ill patients since there is a period that donor cells are present in the patient system. In order to prevent this contamination, several procedures are performed to eliminate white cells from blood, such as irradiation. As our laboratory is a reference center for both diagnosis of genetic disorders and DNA paternity tests, we decide to determine whether STR from different sources can be detected in blood samples from patients that underwent blood transfusion. Samples analyzed were from two different sources. Ten anonymous blood samples were mixed and generated five blood mixtures, each of the in five different dilutions. Besides being tested as a mixture, all these samples were also tested for each marker before being mixed. We also evaluated 20 transfused patients. In this group, patient cells were typed before and up to 7 days after transfusion. In addition, donor cells were also typed prior transfusion. Polymorphic markers tested were D3S1358, D16S539, TH01, TPOX, CSF1PO, and D7S820. DNA isolation was performed from 300μl of each sample using the Wizard® Genomic DNA Purification Kit (Promega), according to manufacture instructions. Regions of interest were amplified by multiplex-PCR using fluorescent primers, using the Applied Biosystems CofilerSTRTM kit. Amplification products were analyzed in ABI PrimÒ 3100 Genetic Analyzer, and GeneScanÒ and GenotyperÒ software. In these samples analyzed in the conditions described above, no microchimerism was identified. We concluded the microchimerism from blood transfusion is unlikely to have major effects on the genotype results of common polymorphisms, even when blood sample is taken within a day after transfusion.  contact: mlpereira@hcpa.ufrgs.br

P-168
Evaluation of allelic alterations in STR in different kind of tumors and formalyn fixed tissues- possible pitfalls in forensic casework.

Margiotta G , Coletti A , Lancia M , Lottanti L , Carnevali E , Bacci M

Section of Legal Medicine, University of Perugia, Terni, Italy.  


Nowadays, the use of formalyn fixed tissue for forensic identification is frequently requested. This is why forensic genetics laboratories must often study normal or tumour tissue specimens that are usually archived with this method.
The somatic instability of tumour tissue on STR (short tandem repeats) loci and the DNA damages caused by formaldeide are well described. These conditions can cause an incorrect allelic determination that makes a forensic identification fail. 
In order to evaluate the real incidence of the genetic alterations caused by somatic instability of tumour tissue, and the incidence of the DNA damages caused by formalyn, we studied 50 specimens of patients who have been operated for neoplasia.
For each patient, we studied a specimen of fresh tumour tissue and a specimen of formalyn-fixed tumour tissue, and the results of these analyses were compared to a specimen of fresh normal tissue and to a specimen of formalyn-fixed normal tissue of the same patient. 







P-169
On-Line Autosomal and Y-STRs Genetic Marker Reference Data Base of Argentina.

Miguel Marino, Andrea Sala and Daniel Corach

Servicio de Huellas Digitales Genéticas and Cátedra de Genética y Biología Molecular. Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires. Junín 956 Ciudad Autónoma de Buenos Aires. Argentina. shdg@ffyb.uba.ar

Autosomal and Y chromosome-specific short tandem repeats (STRs) became the genetic markers of choice for individual identification. In addition, these markers also became powerful tools to assist molecular anthropologists. The availability of internet on-line reference databases may contribute either with forensic scientists or molecular anthropologists to obtain genetic information that may be continuously updated. At the Servicio de Huellas Digitales Genéticas (Genetic Fingerprinting Service, University of Buenos Aires) we constructed an interactive reference database that includes a set of fifteen autosomal STRs (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA) as well as a set of Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393 and DYS385a/b). The complete set of data corresponding to 2003 includes 2710 samples typed with autosomal markers and 239 samples typed with the minimal haplotype (nonaplex)  Y-STRs. The search can be done by choosing all the country or by choosing a particular province. In the database are included 10 provinces: Buenos Aires, Santa Fe, Rio Negro, Chubut, Mendoza, Misiones, Corrientes, Formosa, Chaco and Salta. To evaluate allele or haplotype frequencies in a given province the cursor selects the province from the map of Argentina, the genetic marker is selected by clicking on the ideogram of a metaphase graph in which the markers are located. During July the previous year information is being updated. The frequencies can be determined for a particular year or as combined information. In addition since it is a modular program the number and type of markers can be increased or included. It also includes mutation frequency of the markers described.  This contribution offers a rapid tool for assessing genetic information on-line in order to improve data access.

Contact: shdg@ffyb.uba.ar 

P-170
Population data at fifteen autosomal and twelve Y-chromosome short tandem repeat loci in the representative sample of multinational Bosnia and Herzegovina residents
Marjanovic D1, Bakal N1, Pojskic N1,Drobnic K2, Primorac D3,Bajrovic K1, Hadziselmovic R1
1Institute for Genetic Engineering and Biotechnology, Kemalbegova 10, 71 000 Sarajevo, B&H
2Forensic Laboratory and Research Center, Ministry of the Interior, Stefanova 2, 1501 Ljubljana, Slovenia
3Laboratory for Clinical and Forensic Genetics, University Hospital Split, Spinciceva 1, 21 000 Split, Croatia
In DNA analysis of forensic biological evidence, we have used 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX, FGA) included in the PowerPlex 16â System, as well as twelve Y-chromosomal short tandem repeats loci (DYS19, DYS385a, DYS385b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439) incorporated in the PowerPlexâ Y System, both manufactured by Promega Corp., Madison, WI. Success of this process depends on various factors, but one of the most important is existence of reference database that will create representative picture about molecular-genetic diversity of local population. Therefore, we have tested unrelated healthy individuals born in the Bosnia and Herzegovina, from three main ethnical groups. For the autosomal STR analysis we choose 100 male and female individuals (Bosniacs - 44%, Serbs - 31%, Croats - 17% and others 8%), but for the Y-STR analysis 100 males, voluntary donors, have been tested. Buccal swabs and blood samples (blood spots) have been used as the DNA source. Qiagen DnaeasyTM Tissue Kit was used for DNA extraction. Amplification was carried out as described previously. The total volume of each reaction was 10ml. The PCR amplifications have been carried out in PE Gene Amp PCR System Thermal Cycler (ABI, Foster City, CA) according to the manufacturer’s recommendations. Electrophoresis of the amplification products was preformed on an ABI PRISM 377 genetic analyzer (ABI, Foster City, CA), using 5% bis-acrilamide gel (Long RangerÒ SingleÒ Packs). Raw data have been compiled and analyzed using the accessory software: ABI PRISMÒ Data Collection Software and Gene ScanÒ. Numerical allele designations of the profiles were obtained by processing with Powertyper16 and PowertyperY Macro. Deviation from Hardy-Weinberg equilibrium, observed and expected heterozygosity, power of discrimination and power of exclusion were calculated for autosomal STR loci, as well as exact test of population differentiation. Also, we have compared B&H data with data obtained from geographically closer (neighboring) European populations. In comparison of B&H and southern Croatian data no significant difference (P<0.05) is found at any individual locus. The same statistical parameters are obtained in comparison with pooled Slovenian data. Significant differences (P<0.05) are found at FGA locus in comparative analysis of B&H and pooled Austrian data. In addition, 81 different Y-STR haplotypes: (from total number of 100 obtained) were detected: 69 of them were unique, 7 appeared twice, 4 appeared three and only 1 five times. Allele frequency distribution, the most frequent haplotypes, observed haplotype diversity as well as major allele frequency and gene diversity for the PowerPlexâ Y loci are calculated. Joint result of this study are going to be used as guidelines in additional investigation of genetic relationship between recent B&H and neighboring human populations, originated in our previous studies on Y chromosome bi-allelic markers.     Contact: damir.marjanovic@ingeb.ba 


P-171
Application of Mini-STR Loci to severely degraded casework samples

Martín P 1, Albarrán C 1, García P 1, García O 2,  Alonso A 1

1Instituto Nacional de Toxicología y Ciencias Forenses. Servicio de Biología. Luis Cabrera, 9. 28002 Madrid. Spain
2Area de laboratorio Ertzaintza. Larrauri Mendotxe 18, E-48950 Erandio, Bizkaia, Spain
Two PCR-multiplexes of mini-STR loci (Big Mini multiplex: TH01, FGA, CSF1PO, D21S11, TPOX and D7S820 and Miniplex 5: Penta D, Penta E and D2S1338) (Butler et al.  J. Forensic Sci(2003) 48(5) 1054-1064) have been used to get a nuclear DNA profile from different severely degraded casework biological specimens that generated negative PCR results or partial profiles when commercial STR kits (Identifiler and PowerPlex 16) were employed. These biological specimens included:

-        Bone and soft tissue fragments fixed and long-term storage (3 years) in formalin.
-        Exhumed remains (teeth and compact bone) from a formalin-embalmed cadaver
-        Formalin fixed and paraffin embedded biopsies
-        Old bone remains from mass graves of the Spanish Civil war (1936-1939)

In all cases, mini-STR technology allowed to retrieve additional genetic information with very high efficiency especially for those STR loci with allele sizes less than 150 bp. However, due to the high degradation degree, an extremely peak imbalance was observed between the smaller (60-100 bp) and bigger-sized (120-170 bp) STR markers or even between the smaller and the bigger-sized alleles of the same STR in heterozygote samples. Therefore, in some cases singleplex-PCR amplifications were carried out using different amounts of DNA template and different PCR cycles (28-32 cycles) to improve the quality of STR profiles. On the other hand, different artefactual peaks were observed that were removed by filtration of PCR reactions with Centricon centrifugal devices.
In conclusion, our data indicate that the mini-STR technology is an effective strategy to improve DNA profiling from severely degraded casework human DNA samples that are refractory to amplification of DNA fragments bigger than 200-300 bp. At the present time, we are undertaken a similar study with the new Mini-STR loci recently described by Coble et al. (J Forensic Sci. 2005. 50:43-53)

p.martin@mju.es

P-172
Reference Database of Hypervariable STR
Loci in Entre Ríos Province of Argentina

Martínez GG 1 2, Schaller LC 1, Vázquez LE 1, Bolea M 2 and Martínez Jarreta B 2

1 Servicio de Genética Forense, Superior Tribunal de Justicia, Provincia de Entre Ríos, Argentina.
2 Laboratorio de Genética Forense e Identificación Humana, Universidad de Zaragoza, España.


Allele frequencies of twelve Short Tandem Repeats (STR) loci, CSF1PO, TPOX, TH01, F13A01, FESFPS, vWA, D16S539, D7S820, D13S317, D5S818, F13B and LPL, were determined over six mayor regionally groups in Argentinean province of Entre Ríos. No deviation was observed in the total population analyzed and so in subpopulation for all loci. There was also no evidence of correlation of alleles between loci. The combined matching probability and the combined mean of exclusion chance in Entre Ríos population was 2,44 x 10-13 and 0,99993 respectively. Frequencies, statistical parameters and a filogenetics inference based on distance matrix for all populations group are provided. We analyzed allele frequencies distribution by Pairwise Fst Genetic Distance to construct a tree based on Neighbor-Joining method, and obtained one that is well coincident with their geographical distribution. This study demonstrates that these loci are a useful and convenient tool for forensic identification and parentage testing in this Argentinean province.

P-173
LMD as a forensic tool in a sexual assault casework: LCN DNA typing to identify the responsible

D. Di Martino (1), G. Giuffrè (2),  N. Staiti(1), A. Simone(2), G. Sippelli(2), G. Tuccari(2),  and L . Saravo(1)*

1 Laboratory of Molecular Biology – Raggruppamento Carabinieri Investigazioni Scientifiche (RaCIS), 98128 Messina – ITALY.
2 Department of Human Pathology, University of Messina.

We have previously studied the sensitivity of laser microdissection (LMD) techniques and have tested our capability to yield a complete genotype from 30 aploid sperm cells. Partial but significant genotype information have been obtained also from 5-10 aploid sperm cells. This experimental procedure has important applications both in pathological and in forensic fields. A growing number of sexual assault caseworks occur in the South of Italy, often on behalf of teenagers, and it is more and more important to determine the responsible’s profile, which is usually difficult as biological residuals are mixed and DNA is present in low copy number.
LMD can offer us the chance to distinguish sperm cells of assaulter’s origin from diploid epithelial/ lymphoid cells of victim’s vaginal origin even though both these biological residuals  are present on a solid substrate, like car carpets, sofas, skirts or underwear.
A real casework of a teenager sexually assaulted in a car in a small town in Sicily has induced us to evaluate the possibility to transfer the biological residuals present on a cut off from the car seat to a laser microdissection prepared microscope slide. Biological traces have been former analyzed with Crimescope CS-16 in order to evaluate the kind of traces we were to process; to avoid the loss of the forensic traces, we have reproduced the same conditions in several experimental procedures: we have settled several samples distinct for amount of biological mixed traces, age of the traces and their exposure to different atmospheric agents. DNA typing was performed both with Identifiler STR loci kit and with another forensic kit based on shorter STR amplicons.
Laser microdissection techniques, coupled to high sensitivity DNA typing methods as short STRs,
allows forensic operators to isolate the different cell residuals whenever in front of mixed traces.

Keywords: DNA STR typing; Forensic casework; Mentypeâ, LMD, LCN.
*Corresponding author: rismebiologia@carabinieri.it

P-174
Genetic Population Data from Araraquara region (SP State, Brazil) using PowerPlexÒ 16 Systems Kit

Martins JA, Paneto GG, Pereira GA, Alvarenga VLS, Cicarelli RMB
Laboratório de Investigação de Paternidade, FCF-UNESP, Araraquara, São Paulo, Brazil
Introduction: Because of the fast evolution in molecular biology techniques and in statistical calculations studies, DNA analysis is today the most sensible and specific method for human identification being extremely used in solving most of different forensic cases and paternity tests. As the genetic population data of polymorphic markers are still less known in Brazilian population, the aim of this work was to study allele frequency distributions for the 15 STR loci using PowerPlexÒ16 Systems (Promega) in a population of Araraquara region (SP, Brazil) and to report some statistical parameters of forensic and paternity interest. Methods: Blood samples were obtained from 55 unrelated individuals living in Araraquara region. DNA was extracted using GenomicPrepTM Blood DNA Isolation kit (Amersham). The amplification was performed using PowerPlexÒ 16 Systems kit (Promega) in a PTC-100 PCR Systems (MJ Research), following the manufacturer’s recommendations. The amplified products were run on denaturing 6% polyacrylamide gel in an ABI PRISMÒ 377 DNA Sequencer (Applied Biosystems) and analysed with the GeneScan ver.2.1 analysis software (Applied Biosystems). The frequency of each allele for each locus tested was calculated using the number of observed genotypes in the sample by POWERSTATS ver. 12 (Promega) software. The exact test for the Hardy-Weinberg equilibrium was carried out using GENEPOP ver. 3.4 software and the forensic and paternity parameters (Power of Discrimination, Power of Exclusion, Matching Probability, Polymorphism Information Content, Typical Paternity Index, Observed heterozygosity, Expected heterozygosity) were performed using POWERSTATS ver. 12 and GENEPOP ver. 3.4 softwares. Results and Discussion: After all calculations it was observed that no deviations from Hardy-Weinberg equilibrium were detected for all markers in this study. Moreover, all loci were highly polymorphic and loci as PENTA E (90,5%), TH01 (89,0%), D18S51 (87,2%) and FGA (86,8%) had the highest observed heterozygosities, and the locus TPOX (64%) showed the lowest observed heterozygosity. TPOX also presented lower discrimination power (85,0%) while D18S51 (96,0%), PENTA E (95,92%) and FGA (94,3%) were greater discrimination power systems. The combined power exclusion was 0.99999987, ranging from 0.34 (TPOX) to 0,81 (PENTA E). Conclusion: Results indicated that the 15 loci studied would be useful as genetic markers for forensic identification and paternity testing in Araraquara region

SP, Brazil – contact: cicarell@fcfar.unesp.br


P-175
Distribution of four specific STRs Y-chromosome in Iranian ethnic population

Marvi M1,2 , MirzazadehNafe R1,2 ,Moshiri F2 , Bayat B2 , Mesbah A2 , Sanati MH2 , Mirzajani F2


1) Islamic Azad University of Tehran, Science & Research campus
2) National Institute for Genetic Engineering & Biotechnology


The Y chromosome is one of the smallest human chromosomes , with an estimated average size about 60 million base pairs (Mb).STRs are short tandem repeated arrays with 2-6 bp in length on the Y chromosome and transmitted from father to son’s .
The polymorphism of human Y-specific STRs has an important role in genetic mapping, evolutionary biology, forensic analysis and is very sensitive for genetic drift.
Human genome diversity project in Iran (HGDPI) aims to collect biological samples from different ethnic groups of Iran in order to build up a representative database of human genetic diversity in Iranian population.
In this report we analyzed a set of four Y-STR markers contain: one trinucleotide (DYS 392) and three tetranucleotide (DYS 393, DYS 389I, DYS 389 II) markers in 129 samples from three ethnic groups to determine the allelic frequencies of these markers.      

Contact: nice_roze5408@yahoo.com


P-176
Molecular Genetic Diversity in North India: Forensic and Paternity implications.
Mastana SS1, Papiha SS2 , Sachdeva MP3 , Singh PP4, Singh M4

1Department of Human Sciences, Human Genetics Lab, Loughborough University, Loughborough, UK.
2Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
3Department of Anthropology, Delhi University, Delhi, India;
4Department of Human Biology, Punjabi University Patiala Punjab, India;

The primary objectives of this investigation were to assess level and extent of genetic variation at Minisatellite (VNTRs) Microsatellite (STRs), and ALU Insertion loci in  five endogamous caste populations of the Punjab state, North India,  and to establish a database of allele frequencies which is suitable for population genetic and forensic investigations  As north Indians form a large proportion of migrant population in the UK and Europe, a secondary objective of this study was to assess if there is any subpopulation heterogeneity which could affect the forensic calculations. Blood samples (600) were collected at random from the Jat Sikh, Brahmin, Khatri, Lobana and Scheduled Caste populations. Using standard molecular genetic techniques, we analysed MS1, MS31, YNH24, MS43a VNTRs and HUMTHO1, F13A, F13B, FES, LPL, VWA31 and CSF1PO STRs.  Alu insertion polymorphisms studied included, ACE, TPA, PV92, D1, APO and FXIIIB. General pattern of genetic variation at these highly polymorphic loci is compatible with many European and Indian populations, though some loci have low level of polymorphisms in some populations. Overall efficiency of these loci for forensic and paternity work in Punjabi populations is at par with many Caucasian populations. Average value of PE is more than 0.999 and cumulative PM was extremely low with some variation for different castes. Brahmins, contrary to expectations show higher level of variation at a number of loci. Overall comparisons provided interesting results suggesting caution should be exercised in usage of pooled or general Indian population databases for forensic and paternity investigations.
Address for Correspondence
Dr Sarabjit Mastana
Human Genetics Lab.,
Department of Human Sciences
Loughborough University
Loughborough LE11 3TU.
UK
Tel: 01509223041
Fax: 01509223941

P-177
ALU  Insertion polymorphism variation in India: Genetic Variation and Forensic applications.

Mastana SS1 and  Papiha SS2,

1Department of Human Sciences, Human Genetics Lab, Loughborough University, Loughborough, UK.
2Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.


Alu polymorphisms provide a useful tool to population and forensic geneticists for understanding the population dynamics and its usage in forensics. We report here a study of Alu insertion loci variation from 20 main endogamous caste and tribal populations representing North, Western, Central and East India.  In addition two main populations from Sri Lanka were also analysed. Overall spectrum of variation in these populations is interesting at different geographical and cultural levels. High level of insertion frequencies was observed in some highly inbred groups. Average levels of heterozygosities were found to be relatively high in these populations (range 41% to 49.8%). The genetic diversity coefficient GST among this group of populations was observed to be high (0.049). We also compiled published and unpublished data on other Indian populations to assess the level and extent of genetic diversity at various ethno linguistic, geographic and climatic levels. Overall phylogenetic trees and principal components analysis (PCA) computed from Alu frequencies provide support for socio-cultural and geographical assignment of these populations in Indian population structure. Results are discussed with reference to population origins, forensic applications and human evolution in India using multivariate analyses.
 Address for correspondence:
Dr Sarabjit Mastana
Human Genetics Lab.,
Department of Human Sciences
Loughborough University,
Loughborough LE11 3TU. UK
Tel: 44-1509-223041
Fax: 44-1509-223941

P-178
Dynamics of microsatellite genetic variation in the India: Forensic implications and applications.

Mastana SS 1 , Sun  G 2, Papiha SS 3, Chakraborty R2,Deka R2.
1) Dept Human Sciences, Human Genetics Lab., Loughborough University, Loughborough, England;
2) Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267. USA;
3) Department of Human Genetics, University of Newcastle on Tyne. England.

We have analysed genetic variation at 13 STR loci (CODIS core loci) in a sample of 16 ethnically and geographically diverse endogamous caste and tribal populations of the India. A wide spectrum of allelic distribution at different loci was observed in different geographical and ethnic populations. Overall populations within geographical regions showed greater degree of similarity. Statistically significant differences were observed in a large number of inter-population comparisons. FGA, D18S51 and D21S11 loci were the most polymorphic in a majority of populations. FGA locus had the highest average heterozygosity (86%) and the lowest was observed for TPOX (69%). Average heterozygosity for all loci was 0.79. Coefficient of genetic diversity showed a narrow range for different loci (0.007 to 0.026) with an average of 1.4%, which indicates that these populations are at an early stage of micro-differentiation. Phylogenetic trees and principal component analysis computed from microsatellite allele frequencies provide support for socio-cultural and geographical assignment of these populations.  Lowest match probability and highest exclusion probability was observed for the FGA locus in majority of the populations. Combined match probability was low (1.55E-15 to 7.47E-16), and combined exclusion probability was > 99.999%. There was no evidence of association of alleles between loci studied, so these loci seem to comprise a suitable group of markers for population genetic purposes and for paternity and forensic testing.
This research was supported by NIH grant GM45861, NIJ grant 98-LB-VX-002 and funds from Loughborough University.

Address for Correspondence
Dr Sarabjit Mastana
Human Genetics Lab.,
Department of Human Sciences
Loughborough University
Loughborough LE11 3TU.
UK
Tel: 01509223041
Fax: 01509223941

P-179
Introduction of DNAase in forensic analyses

Melean G, Ricci U, Genuardi M

Azienda Ospedaliera-Universitaria “A.Meyer”, U.O. Genetica Medica, Florence, Italy

Laboratory DNA contamination (plastic, tube etc.) is a frequent problem in forensic genetics, especially when extra PCR cycles are used to obtain acceptable amplified products from low copy number DNA samples. Many authors have suggested that the use of DNAase may reduce the possibility of DNA contamination, but this approach is normally limited for anthropological DNA analysis. Here, we have evaluated the use of the DNAase in combination with a commercially available kit for forensic genetics study.
Initially, we introduced 1 ng genomic DNA in the manual amplification mix without primers in order to simulate DNA contamination. The contaminated mix was incubated with DNAase at different temperatures to obtain the optimal action time of the enzyme. Different times and temperatures of DNAase inactivation were also tested to obtain the most efficient inactivation conditions. The primers were added only after DNAase inactivation to avoid their degradation. The PCR reaction was performed without adding any DNA, following the indication of the authors, using 40 cycles of amplification. PCR products were analysed by electrophoresis in a vertical polyacrylamide gel in an automated DNA sequencer (LICOR IR2 4200 DNA sequencer). Inactivation times were considered effective when no amplification was observed. Inactivation times and temperatures were considered effective when the primer’s band was evident in the polyacrilamide gel.
Using optimal values obtained in the first experiment, we performed the amplification of low copy number DNA samples, quantified by Real-Time PCR, recovered from gloves and objects touched by known donors. The same experiments were applied using the commercial kit AmpFlSTR® Profiler Plus™ (Applied Biosystems), with and without DNAase, using 34 cycles of amplification. The use of DNAase in these conditions didn’t modify the efficiency of the PCR.
We argue that the use of DNAase may be useful to reduce the possibility of laboratory DNA contamination when low copy number DNA samples are amplified. In these situations, introduction of the DNAase may be possible considering that the optimal conditions, found in the present work, are easily applicable in standard PCR protocols.


P-180

Flemish population genetic analysis using 15 STRs of the Identifiler® kit

Mertens G, Mommers N, Cardoen E, De Bruyn I, Jehaes E, Rand S, Van Brussel K, Jacobs W
Forensic DNA Laboratory, Antwerp University Hospital, B-2650 Edegem, Belgium
Allelic frequencies for the short tandem repeat systems CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, vWA, FGA, TH01, TPOX, D2S1338 and D19S433 were determined in a Flemish population sample of 231 individuals, using the Identifiler kit (Applied Biosystems). No deviations from Hardy-Weinberg equilibrium were observed. Combined, the 15 loci yield a Matching Probability of 1 in 111 ´ 1012 and a Power of Exclusion of 99.999995 %.
1.       Introduction
The aim of this study was to establish a database of the Flemish, i.e. the Dutch speaking population of the northern half of Belgium. We therefore applied the AmpFlSTR Identifiler PCR Amplification (Applied Biosystems) kit, that co-amplifies the 13 Combined DNA Index System (CODIS) STR loci (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, vWA, FGA, TH01, TPOX) and in addition the two tetrameric markers D2S1338 and D19S433, as well as the amelogenin locus for gender identification. Here we present the allelic frequencies and parameters of forensic efficiency in a sample of 231 unrelated Flemish individuals.
2.       Material and Methods
Buccal swabs were collected from 231 unrelated Flemish individuals, representing the mother (115 females) or alleged father (116 males) from paternity cases.  DNA was extracted using the Qiamp DNA kit (Qiagen). PCR amplification and subsequent capillary electrophoresis were performed according to the manufacturer’s manual, on the PE 9700 thermal cycler (Applied Biosystems) and the ABI 3100 Genetic Analyzer (Applied Biosystems) respectively. Alleles were named according to the recommendations of the DNA Commission of the International Society for Forensic Genetics [1]. Allelic frequencies were estimated by direct gene counting. Conformity of the observed genotype frequencies with Hardy-Weinberg expectations (HWE) was examined by the exact test from Guo and Thompson [2] using the Arlequin software [3]. The parameters relevant for forensic casework (matching probability, power of exclusion, mean paternity index and polymorphism information content) were determined using the Powerstat worksheet (Promega).
3.       Results and Discussion
Allelic frequencies in the Flemish population sample typed for the 15 Identifiler STRs are given in Table 1; results of testing for HWE and the statistical parameters of forensic interest are shown in Table 2. Regarding the test results for HWE, a p value > 0.05 was obtained for all STRs except one. For D7S820 the exact test yielded a p value of 0.015. To judge whether to reject the null hypothesis (population equilibrium) based on the magnitude of the smallest of multiple p values, it is necessary to apply the Bonferroni [4] correction to the chosen significance threshold, which is typically 0.05. Considering the Bonferroni procedure and the fact that 15 tests for HWE were simultaneously performed on the same population sample, the significance threshold is adjusted from a = 0.05 to a = 0.05 / 15 = 0.0033 which is clearly below the p value of 0.015 that was observed for D7S820. Hence this single p value gives no reason to reject the null hypothesis.
Combined, the 15 STRs result in a Matching Probability of 1 in 111 ´ 1012 and a Power of Exclusion of 99.999995 %, which should be effective in the resolution of most forensic and paternity cases.
References
[1]               W. Bär, B. Brinkmann, B. Budowle, A. Carracedo, P. Gill, P. Lincoln, W. Mayr, B. Olaisen, DNA recommendations - Further report of the DNA commission of the ISFH regarding the use of short tandem repeat systems, Int. J. Legal Med. 110 (1997) 175-176.[2] S.W. Guo, E.A. Thompson, Performing the exact test of Hardy-Weinberg proportion for multiple alleles, Biometrics 48 (1992) 361-372. [3]S. Schneider, D. Roessli, L. Excoffier (2000) Arlequin ver.2000: A software for population genetic data analysis. Genetics and Biometry Laboratory, University of Geneva, Switserland http://anthro.unige.ch/arlequin [4]C.E. Bonferroni, Teoria statistica delle classi e calculo delle probabilita, Pubblicazioni del Instituto Superiore di Scienze Economiche e Commerciali de Firenze 8 (1936) 3-62. Contact: Gerhard.Mertens@uza.be

P-181
Polymorphisms of 4 Y-chromosome STRs in three ethnic groups of Iran


MirzazadehNafe R1,2,Marvi M .1,2,Bayat B2,Moshiri F2, Mesbah SA2,Sheydaie M1, Sanati MH2 , Mirzajani F2


1-Science &Research Campus, Islamic Azad university of Tehran
2- National Institute for Genetic Engineering & Biotechnology



Y-chromosomal microsatellites or short tandem repeats (STRs) are of increasing interest in paternity testing, forensic casework, anthropological and evolutionary studies. This study reports Y-chromosome STR allele frequencies data in three Iranian ethnic groups. Four Y-chromosome STRs (DYS19, DYS388, DYS390and DYS391) have been analyzed in 129 males from these ethnic groups in three provinces (Azerbaijan,Fars and Kurdistan)of Iran.

Contact: r_nafe@yahoo.com 

P-182
Amelogenin Y negative males: multiple origins

Mitchell RJ1, Kreskas M1,2, Baxter E1,2, Buffalino L1,2, van Oorschot RAH2

1Department of Genetics and Human Variation, La Trobe University, Victoria 3086, Australia
2Victoria Police Forensic Services Department, Victoria 3085, Australia


Many forensic laboratories routinely test for gender of a biological sample by typing for an Amelogenin sequence that is incorporated in many of the DNA profiling kits. Amelogenin is a locus found on both X and Y chromosomes but differs in size and sequence which allows the alleles to be distinguished. Occasionally a sample known to be from a normal male is scored as a female ie X allele only, i.e. Amelogenin Y negative. It is of interest to know if this phenomenon results from primer mismatch(es) or deletions and if the mechanism is the same for all such samples.
We tested five Amelogenin Y negative male samples with a series of DNA markers on Yp to determine the approximate size of the deletion(s) as well as with STRs to determine the Y haplotypes associated with these samples to evaluate their level of relatedness.
We show that there are at least two different deletions that cause the phenomenon. A deletion of 304 to 731Kbp was identified in two samples and a deletion of 712 to 1001Kbp was identified in the other three samples. Each sample had a different Y 11-locus haplotype. Whereas the haplotypes of the samples with the smaller deletion were closely related/similar to each other, one of the haplotypes of the samples with the larger deletion was very distant from the other two. These data suggest that Amelogenin Y negative males have arisen through multiple, independent evolutionary events.
Whilst Amelogenin Y null males are rare, routine screening of forensic samples of unknown gender for the presence of the Y chromosome, using other methods, should be considered.


P-183
Validation of five X-chromosomal STR DXS6800, DXS6807, DXS6798, DXS8377 and DXS7423 in an Antioquian population sample

Moreno MA1,2, Builes JJ1,2, Jaramillo P2, Espinal C1, Aguirre D1, Bravo MLJ1

1Genes Ltda. Medellín-Colombia.
2Instituto de Biología, Universidad de Antioquia. Medellín–Colombia.


The X linked short tandem repeats (STR) markers have proven to be very useful tools for paternity testing when the disputed child is female.
The aim of this study was to describe the polymorphism of five X-chromosomal STR loci (DXS6800, DXS6807, DXS6798, DXS8377 and DXS7423) in an Antioquian (Colombian) population sample, and evaluate their efficiency in forensic practice and paternity testing.
PCR products were separated in 4% acrylamide-bis-acrylamide denaturing gels followed by silver staining.  Allele size determination and genotyping were performed according to recommendations of the DNA Commission of the International Society of Forensic Genetic using the allelic ladder manufactured at home and based on DNA controls including K562 (Promega Corporation) and 1331-1, 1331-2, CEPH family members.  Gene and haplotype frequencies were calculated using ARLEQUIN version 2000.
Population genetic data were obtained by analyzing 300 unrelated males from Antioquian (Colombian) population. The comparisons of the allele frequencies distributions for Antioquia population are similar to Europe populations. The forensic efficiency values demonstrate that especially DXS8377 and DXS6798 are highly informative markers for kinship analysis and deficiency cases

 

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