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Materials and methods

Chapter 1: Autosomal markers

2. Materials and methods 1. DNA Samples

3.4. Inter-population variability

AMOVA analysis of the six Jewish populations studied showed a low but statistically significant value (FST = 0.00871; p < 10-5). Interestingly, pairwise comparisons (Supplementary Table S6) evidenced the existence of a sub-set composed of the Jewish populations (Sephardic, North Africa, Mizrahim and Ashkenazi) with non-significant genetic distances, whereas the converted Jewish populations (Bragança Jews and Chuetas) presented significant differences with all other populations tested in this study. However, hierarchical AMOVA showed lack of homogeneity within these sub-sets (FSC = 0.00250; p

= 0.01075).

A comparison was also performed between the populations in this work and other populations previously studied for the same set of Indel markers (Portugal, Angola, Mozambique, Macau and Taiwan (Pereira et al., 2009), South East Spain (Saiz et al., 2014), Brazil (Rio de Janeiro and Terenas) (Manta et al., 2012), and Majorca (Chueta’s host population) (GHEP-ISFG collaborative exercise

www.gep-isfg.org/en/working-79

commissions/collaborative-exercise-indels-2012.html). MDS results (stress value <0.199) showed greater structure than would be obtained from a random dataset (Sturrock and Rocha, 2000). The MDS plot (Figure 1) indicated that European, African and Asian populations are distantly positioned. Terenas (with major Amerindian ancestry living in Mato Grosso do Sul, Center-West Brazil) was closer to the Asians, while Rio de Janeiro was placed between Europe and Africa, as expected due to their origin. Jewish and South European populations (Portugal, Majorca and South East Spain) clustered together, indicating that this set of markers can separate efficiently between populations from different continents, but does not appear to be a suitable tool for studying the genetic sub-structure in Mediterranean context.

Figure 1. Multidimensional Scaling (MDS) plot of the pairwise genetic distances between the 6 populations with Jewish ancestry (showed as circles) in this study and South European populations (Portugal, South East Spain and Majorca), Brazilian populations (Rio Janeiro and Terenas), Asian and African populations. All non-Jewish populations are shown as black squares.

Within the Mediterranean region, taking into account the genetic distances matrix (Supplementary Table S6), we can observe two groups without significant differences within them; one is the aforementioned Jewish group, and the other includes the South European non-Jewish populations (Portugal, Majorca and South East Spain). North African Jews showed no significant distances with any population of any group. Regarding the converted Jewish populations, Chuetas presented significant differences with all other populations, including both the Jews and their host population, Majorca; but Braganza Jews were not significantly different to Portugal, their host population.

A Bayesian clustering analysis was performed with the same samples in STRUCTURE software in order to deeper scrutinize the substructure of the Mediterranean region for this set of 38 neutral, slow evolving, autosomal markers. The results consistently revealed

80

worse ln P(D) values for K>1 (Supplementary Figure 1), failing to detect distinct clusters in the data set and supporting that any possible genetic structure in the populations here analyzed could not be discerned with the level of resolution afforded by these 38 loci.

4. Conclusions

This study provides a useful database of the 38 Indel multiplex (Pereira et al., 2009) for populations with Jewish ancestry including two Sephardic isolates, the Chuetas and the Crypto-Jews from Bragança. The results obtained demonstrated also their usefulness for general forensic purposes, especially in situations where conventional STRs may result in low paternity indices. However, this set of markers does not seem adequate for molecular anthropology studies in subcontinental level, namely in the Mediterranean region.

It is important to highlight that although the genetic distances between Jewish populations were low, significant differences were observed for both Chuetas and Bragança Jews with the others. Therefore, specific databases for these Jewish populations must be used in the forensic field to correctly weigh the value of the evidence based on these Indel markers.

This study follows the guidelines for publication of population data proposed by the journal (Carracedo et al., 2013).

Acknowledgments

This work was partially supported by grant AAEE24/2014 from the Direcció General de R + D + I (Comunitat Autònoma de les Illes Balears) and European Regional Development Fund (ERDF). RP (SFRH/BPD/81986/2011) and IN (SFRH/BD/73336/2010) are recipients of grants awarded by the Portuguese Foundation for Science and Technology (FCT) and co-financed by the European Social Fund (Human Potential Thematic Operational Programme –POPH).

B01 rs34541393 0.3585 0.4167 0.2778 0.3182 0.4191 0.3091

B01 rs34541393 0.4599 0.4861 0.4012 0.4339 0.4869 0.4271 0.4481 ± 0.0314

MP PD PIC PE TPI MP PD PIC PE TPI MP PD PIC PE TPI MP PD PIC PE TPI MP PD PIC PE TPI MP PD PIC PE TPI

MP: Matching probability; PD: Power od discriminations; PIC: Polymorphism Information Content; PE: Power of Exclusion; TPI: Typical Paternity Index.

Autosomal STR

Alleged

Father Daughter Mother X-STR Alleged

Father Daughter Mother Indels Alleged

Father Daughter Mother Indels Alleged

Father Daughter Mother

D8S1179 13-14 11-14 11-14 DXS10103 18 17-18 17-20 B01 22 12 11 Y01 12 12 12

D21S11 30-32.2 30 30-32.2 DXS8378 10 10-11 11-12 B02 11 11 11 Y02 22 12 12

D7S820 11-13 12-13 12-13 DXS7132 15 13-15 13-14 B03 12 12 22 Y03 12 12 12

CSF1PO 11 11-12 11-12 DXS10134 37 36-37 36-37 B04 11 12 12 Y04 22 22 22

D3S1358 16 16-17 16-17 DXS10074 14 14-19 17-19 B05 11 12 12 Y05 11 11 12

TH01 9.3 9.3 8-9.3 DXS10101 32 31-32 29.2-31 B06 12 12 22 Y06 12 11 11

D13S317 12 12 12-13 DXS10135 21 21-25 25-26 B07 12 11 11 Y07 22 12 12

D16S539 11-13 9-11 9 DXS7423 15 15 15 B08 12 11 11 Y08 11 11 12

D2S1338 17-22 18-25 23-25 DXS10146 30 27-30 27-46.2 B09 11 12 22 Y09 22 12 12

D19S433 13 13-15 13-15 DXS10079 20 20 19-20 B10 22 22 22 R01 22 12 12

VWA 17-18 16-17 16-18 HPRTB 12 12-14 13-14 G01 11 12 22 R02 11 11 11

TPOX 11 9-11 8-9 DXS10148 26.1 26.1 26.1-27.1 G02 22 12 11 R03 11 11 11

D18S51 13-16 13-14 14-15 G03 22 12 12 R04 12 12 12

D5S818 11-13 11-12 11 G04 22 22 12 R05 22 12 11

FGA 21-22 21 21-23 G05 12 22 22 R06 12 11 11

Penta E 5-10 10-11 10-11 G06 12 22 12 R07 11 11 12

Penta D 10-12 10-11 10-11 G07 12 12 11 R08 12 12 22

G08 12 12 11 R09 22 22 22

G09 12 22 22 R10 22 22 22

Mismatches in autosomal STR markers are labelled in bold.

Sephardic Jews

North African Jews

Ashkenazi Jews

Middle Eastern Jews

Bragança

Jews Chuetas Majorca (Spain)1

South East

Spain2 Portugal3 Rio Janeiro

(Brazil)4 Asia3 Terenas

(Brazil)4 Africa3 Sephardic Jews 0

North African Jews 0 0

Ashkenazi Jews 0.00259 0.00498 0

Middle Eastern Jews 0.00212 0.00472 0.00439 0

Bragança Jews 0.00842 0.00714 0.00942 0.01367 0

Chuetas 0.0112 0.01004 0.01509 0.01714 0.00835 0

Majorca 0.00588 0.00456 0.00637 0.01205 0.00497 0.01188 0

South East Spain 0.00307 0.00249 0.00702 0.01009 0.00522 0.00586 0.00157 0

Portugal 0 0 0.0021 0.006 0 0.00325 0 0 0

Rio Janeiro 0.01309 0.01453 0.01351 0.01639 0.0101 0.01557 0.01533 0.01313 0.00418 0

Asia 0.07783 0.08834 0.0709 0.07665 0.08979 0.08226 0.08393 0.08275 0.08862 0.062 0

Terenas 0.09512 0.10289 0.09741 0.09528 0.08938 0.09383 0.10614 0.09656 0.09056 0.06601 0.09143 0

Africa 0.10134 0.11246 0.10343 0.10934 0.09564 0.10088 0.10607 0.10161 0.10564 0.04784 0.12031 0.13971 0

1 Unpublished data; 2 Saiz et al. (2014); 3 Pereira et al. (2009); 4 Manta et al. (2012).

Non-significant distances (p>0.00385) are labelled in bold. Darker colours correspond to higher genetic distances.

Jews, Chuetas and Bragança Jews).

K Ln P(D) Var [Ln P(D)]

1 -24433.93 18.97

2 -25073.31 1381.39

3 -25509.92 2314.4

4 -26072.43 3483.98 5 -26650.01 4729.99 6 -26219.53 3875.16 7 -27361.11 6250.36 8 -27792.25 7157.95 9 -29455.56 10523.74

Supplementary Figure 1b. STRUCTURE Plots for 13 worldwide populations. K=4 showed the high value of ln P(D). In K=7 Terenas population (Native American) appears as a separated cluster

K=4

K=7

1: Sephardic Jews; 2: North African Jews;3: Middle Eastern Jews; 4: Ashkenazi Jews; 5:Chuetas; 6:Braganza Jews; 7: Majorca (Spain); 8:South East Spain; 9: Portugal; 10:

African; 11: Asian; 12: Terenas and 13: Rio de Janeiro (Brasil).

Chapter 2: X-Chromosome