Ethical Considerations

When gonosomal aberrations or instances of testicular feminisation are detected, ChrX typing is no longer a valid means of kinship testing. In any case, it appears worthwhile emphasising that such findings, when inadvertently obtained during kinship testing, come under the duty of confidentiality. Disease-relevant information should not be revealed to an affected individual unless they explicitly ask for it.

In several countries, such as Germany, it is assumed by forensic scientists that forensic DNA testing should not disclose diseases or genetic risks. This policy complies fully with STR typing strategies utilizing well established autosomal STRs, such as the CODIS markers, Y-chromosomal (ChrY) markers, mtDNA analysis and nearly all established X-chromosomal (ChrX) markers. ChrY and mtDNA typing may reveal some general information as to a person's ethnic origin, however, this cannot be considered as an intervention into the person's privacy.

This would in principle apply to gender identification typing ChrX and ChrY markers, too. However, usage of ChrX markers might reveal chromosomal aberrations such as the Klinefelter Syndrome. This complex disorder is linked to an chromosomal genotype of 46XXY or other numerical aberration of the ChrX and may be recognised by heterocygocity of ChrX markers in a male person. Genotype X0 is associated with the Ullrich-Turner syndrome. This may be diagnosed when females show (virtual) homogosity in all ChrX STRs investigated.

Furthermore, there is the Androgen Insensitivity Syndrome (also known as Testicular Feminization Syndrome; Androgen Receptor Defieciency or Dihydrotestosterone Receptor Deficiency) which can be diagnosed when a person’s female phenotype is not linked to a female genotype (XX) but a male one (XY).

We announce here that our group no longer considers HumARA a suitable DNA marker in forensic casework.

Desmarais et al. [1] have used HumARA typing as a starting point to generate specialized formulae for ChrX typing in forensic practice. Hence, these markers are well established in forensic DNA typing. However, it has been known from the very beginning of HumARA testing that the HumARA CAG repeat, in contrast to all other forensic DNA markers, is located in a coding region (androgen receptor gene, exon 1). This means the repeat codes for a polyglutamine tract. La Spada et al. [2] proved that X-linked spinal and bulbar muscular atrophy (SBMA) is attributable to a mutation at this locus; the disease occurs when there are trinucleotide repeat lengths of more than 43 bp.

Apart from the SBMA disease, HumARA typing can detect a number of further health risks, such as an increased risk of impaired spermatogenesis and increased risks of breast, endometrial, colorectal, and prostate cancer.

1. Desmarais D, Zhong Y, Chakraborty R, Perreault C, Busque L (1998) Development of a highly polymorphic STR marker for identity testing purposes at the human androgen receptor gene (HUMARA). J Forensic Sci 43: 1046-1049.
2. La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77-79.