Mutation Rates With Ystr Markers

Several studies have been conducted to examine mutation rates among the commonly used Y-STR loci. Most studies have focused on the minimal haplo-type loci. Two different approaches have been used: deep-rooted pedigrees (Heyer et al. 1997, Bonne-Tamir et al. 2003) and male germ-line transmissions from confirmed father/son pairs (Bianchi et al. 1998, Kayser et al. 2000, Dupuy et al. 2001, Dupuy et al. 2004, Kurihara et al. 2004). The pedigree approach has the advantage of not having to run as many samples but when differences are seen it can be hard to attribute the mutation to the proper generation (see Bonne-Tamir et al. 2003) or to potential illegitimacy (Heyer et al. 1997). Heyer et al. (1997) tested only 42 males but were able to infer information from 213 generations or meioses (once three illegitimate lines had been removed) while Bonne-Tamir et al. (2003) examined 74 male samples that spanned 139 generations. Of course the pedigree approach requires detailed genealogical records and no breakdown in the paternal lineages through illegitimacy.

The mutation rates for Y-STRs are in the same range as autosomal STRs, namely about 1-4 per thousand generational events (0.1-0.4%) (see Chapter 6). Table 9.6 includes a summary of mutation rate studies on the minimal haplotype loci. A compilation of the various studies reveals that compound repeat locus DYS390 is the most likely to mutate with DYS392 being the least likely to change. As with autosomal STRs, single repeat changes are favored over multiple repeat jumps. Allele gains are more common than allele losses as the mutations occur with not only locus-specific but also allele-specific differences in mutation rate (Dupuy et al. 2004). Mutations typically only occur when 11 or more homogeneous repeats are immediately adjacent to one another (Kayser et al. 2000).

Locus

No. of Mutations/ Reference

Summed Mutation

No. of Meioses

Rate for Locus

0/249 Bianchi et al. (1998)

0/139 Bonne-Tamir et al. (2003)

0/249 Bianchi et al. (1998)

1/139 Bonne-Tamir et al. (2003)

1/139 Bonne-Tamir et al. (2003)

DYS389II 4/1766 Dupuy et al. (2004) 11/3103 =

0/249 Bianchi et al. (1998)

0/139 Bonne-Tamir et al. (2003)

0/249 Bianchi et al. (1998)

2/139 Bonne-Tamir et al. (2003)

0/249 Bianchi et al. (1998)

2/139 Bonne-Tamir et al. (2003)

0/249 Bianchi et al. (1998)

0/139 Bonne-Tamir et al. (2003)

Table 9.6

Summary of mutation rates observed in Y-STRs studies.

Table 9.6 (Continued)

0/249 Bianchi et al. (1998)

0/139 Bonne-Tamir et al. (2003)

Kayser and Sajantila (2001) discuss the implications of mutations for paternity testing and forensic analysis. They observed mutations at two Y-STRs within the same father/son pair suggesting that differences at three or more Y-STRs are needed before an 'exclusion' can be declared with paternity testing or kinship analysis, which is typically the same criteria used for paternity testing with autosomal loci (see Chapter 23).

Occasionally duplications or even triplications of a Y-STR locus have been reported, particularly for DYS19. It is important to keep this fact in mind so that two peaks at the DYS19 locus are not automatically interpreted as coming from a mixture of two males. Both of these issues, namely mutations impacting paternity analysis and duplications of loci potentially confusing mixture interpretation, suggest that analysis of additional Y-STR loci can be helpful in these situations.

ISSUES WITH USE OF Y-STRs IN FORENSIC CASEWORK

Y-STR assays have been used for several years on a limited basis to aid forensic casework. Their use has been much more widespread in Europe than the United States. Early work in the U.S. with Y-STRs was performed in the late 1990s by the New York City Office of the Chief Medical Examiner (OCME). ReliaGene Technologies, Inc. (New Orleans, LA) developed the first Y-STR kit and started doing Y chromosome testing in late 2000.

The New York City Office of the Chief Medical Examiner primarily uses Y-STR testing when any one of the four scenarios is met (Prinz 2003): (1) evidence is positive for semen but no DNA foreign to the victim can be detected, or potential male alleles are below the detection threshold with autosomal STR tests; (2) the evidence in question is amylase positive and a male/female mixture is expected; (3) a large number of semen stains need to be screened; and (4) the number of semen donors need to be determined (e.g., suspected gang rape).

There have been several published reports describing the use and value of Y-STR testing in forensic casework. Some of these published results are summarized in Table 9.7.

Locus

No. of Mutations/ Reference

Summed Mutation

No. of Meioses

Rate for Locus

Kit/Loci Used

Reference

Comments

In-house assay with DYS19, DYS390, DYS389I/II

Prinz et al. (2001) In one year at the New York City Office of the Chief Medical Examiner, Y-STR testing was performed in more than 500 cases with over 1000 evidence and reference samples examined. A full or partial profile was obtained on 81% of all tested evidence samples (740 worked/915 samples tested). Mixtures of at least two males were observed in 97 instances. In male/female mixtures of up to 1:4000, the male component could be cleanly detected.

In-house assay with 9 Y-STR loci amplified in 3 PCR reactions

Dekairelle and Y-STR typing was attempted on 166 semen traces from 89 cases Hoste (2001) that failed to yield a detectable male autosomal profile following differential extraction. About half of the cases had sufficient DNA to produce a Y-STR profile.

In-house assay with DYS393, DYS389I/II

Sibille et al. (2002) Y-STR results could still be obtained more than 48 hours after the sexual assault in 30% of the cases examined. In 104 swabs collected with no evidence of sperm, Y-STRs could be detected in ~29% of the samples tested.

In-house assay with DYS19, DYS390, DYS389I/II

Y-PLEX 6 and Y-PLEX 5 kits

Prinz (2003) Six case studies are reviewed along with advantages and disadvantages of Y-STR testing in each case: (1) different semen donors on vaginal swab and underwear; (2) possible oligospermic perpetrator gave a nice Y-STR profile but failed to have a 'male' fraction with differential extraction; (3) oral intercourse with no autosomal results - not possible to enrich male cell fraction with differential extraction in cases involving saliva; (4) presence of multiple semen donors created a complex autosomal mixture that could be sorted out with Y-STR results; (5) sperm cell fraction lacked amelogenin Y-specific peak due to known deletion - Y-STR results confirmed that the sperm cell fraction DNA was of male origin; and (6) Y-STR testing was used to rapidly screen 18 semen stains for comparison to five suspects and thus save the time of performing the differential extraction

Sinha (2003) Five cases are reviewed: (1) criminal paternity case with a male fetus where the alleged father could not be excluded as the biological father; (2) autosomal STR test resulted in an uninterpretable mixture -suspect was excluded at three of the seven Y-STR loci tested; (3) Y-PLEX 6 STR profile matched suspect with sweat stains on cloth found at crime scene; (4) fingernail cuttings from a victim matched a suspect at 11 Y-STR loci while another suspect was excluded at two loci; (5) semen positive stain with no sperm cells produced a Y-PLEX 6 profile consistent with the male suspect

Y-PLEX 6 and Y-PLEX 5 kits

Sinha et al. (2004) Seven cases are reviewed (some are the same as Sinha 2003) and a list of cases where Y-STR results have been accepted in U.S. courts is provided.

ReliaGene reported use of Y-STRs on 188 forensic samples from 2000-2003 with their Y-PLEX™ 6 and Y-PLEX™ 5 kits (Sinha et al. 2004). Samples were from epithelial cells including azospermic seminal fluid, sweat or saliva, sperm, fingernails, blood, and other tissues. Y-STR testing has been accepted in several jurisdictions throughout the United States (Sinha et al. 2004).

Determining the amount of male DNA present rather than the total amount of male and female DNA is important to getting on-scale results with Y-STR testing.

Table 9.7

Some published reports describing use of Y-STRs in forensic casework.

One approach is to estimate the general level of male DNA present by assessing the strength of the p30 antibody signal (see Chapter 3) (Prinz 2003). The recent availability of real-time PCR assays specific to the male DNA component of a forensic mixture (e.g., Quantifiler Y kit) provides a more high-tech approach.

Duplications or triplications of several Y-STRs have been reported for DYS19, DYS390, and DYS391. For example, one study found nine duplications for DYS19 in 7772 individuals (Kayser et al. 2000). Triplicated DYS385 alleles have also been reported (Kayser et al. 2000, Butler et al. 2002, Kurihara et al. 2004). These possible multi-allelic patterns need to be kept in mind so that a mixture is not expected when encountering multiple alleles at a single locus that could legitimately come from a single-source sample (see Chapter 7).

Y-SNP AND BI-ALLELIC MARKERS

Single nucleotide polymorphisms, Alu insertions, and insertion/deletion markers exist on the Y chromosome just as they do throughout the rest of the human genome (see Chapter 8). Most of the focus to date in forensic DNA typing applications has been on Y-STRs rather than Y-SNPs due to the higher power of discrimination with the multi-allelic Y-STRs. Y-SNPs play an important role in human migration studies though because they enable effective evaluation of major differences between population groups.

Y-SNP alleles are typically designated as either 'ancestral' or 'derived' and can be recorded in a simple binary format of 0 or 1 for ancestral and derived, respectively. The ancestral state of a Y-SNP marker is usually determined by comparison to a chimpanzee DNA sequence for the same marker (Underhill et al. 2000).

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