Leukemia specific loss of heterozygosity of MHC in a CLL patient: Disease state impacts timing of confirmatory typing

Coppage, Myra; Iqbal, Anwar; Aḥmad, Auṣāf; Becker, Michael W.

doi:10.1016/j.humimm.2012.10.003

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…On the other hand, since HLA testing is often performed at first diagnosis or progression of disease, the patients' samples often exhibit high blast contents, rendering them susceptible to actual “blast typing.” In accordance with other authors we identified pretransplant HLA-LOH as a pertinent source of error for the patients' HLA typing [4, 6–10]. As exemplified, the detection of primary HLA-LOH is tricky and might result in false HLA-typing.…”

Section: Discussionsupporting

confidence: 88%

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Combination of Complement-Dependent Cytotoxicity and Relative Fluorescent Quantification of HLA Length Polymorphisms Facilitates the Detection of a Loss of Heterozygosity

Witter¹,

Reibke

Subklewe

et al. 2014

Bone Marrow Research

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Loss of heterozygosity (LOH) is a common event in malignant cells. In this work we introduce a new approach to identify patients with loss of heterozygosity in the HLA region either at first diagnosis or after HLA mismatched allogeneic HSCT. Diagnosis of LOH requires a high purity of recipient target cells. FACS is time consuming and also frequently prevented by rather nonspecific or unknown immune phenotype. The approach for recipient cell enrichment is based on HLA targeted complement-dependent cytotoxicity (CDC). Relative fluorescent quantification (RFQ) analysis of HLA intron length polymorphisms then allows analysis of HLA heterozygosity. The approach is exemplified in recent clinical cases illustrating the detection of an acquired allele loss. As illustrated in one case with DPB1, distinct HLA loci in donor and patient were sufficient for both proof of donor cell removal and evaluation of allele loss in the patient's leukemic cells. Results were confirmed using HLA-B RFQ analysis and leukemia-associated aberrant immunophenotype (LAIP) based cell sort. Both results confirmed suspected loss of HLA heterozygosity. Our approach complements or substitutes for FACS-based cell enrichment; hence it may be further developed as novel routine diagnostic tool. This allows rapid recipient cell purification and testing for loss of HLA heterozygosity before and after allogeneic HSCT in easily accessible peripheral blood samples.

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Section: Discussionsupporting

confidence: 88%

“…In addition, loss of HLA heterozygosity was also described prior to any treatment [4, 6–10] in malignant cells, which might be a serious confounder in a patient's HLA typing. Despite its vital importance, copy number neutral loss of heterozygosity is easily missed by standard methods.…”

Section: Introductionmentioning

confidence: 99%

Combination of Complement-Dependent Cytotoxicity and Relative Fluorescent Quantification of HLA Length Polymorphisms Facilitates the Detection of a Loss of Heterozygosity

Witter¹,

Reibke

Subklewe

et al. 2014

Bone Marrow Research

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“…In addition, heterozygote advantage is the main mechanism of balancing selection, which means an individual who is heterozygous at a particular gene locus has a greater fitness than an individual homozygous at the same locus (Eugenie, 1978). Studies have shown that high genetic variance and heterozygote advantage can support a high survival rate, particularly in immune regions of genes (Daum et al, 2012;Eizaguirre et al, 2012;Coppage et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Evidence of balancing selection in multiple indigenous chicken populations

Arlud

Zeng

2016

Genet. Mol. Res.

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ABSTRACT. Microsatellite DNA markers, which are assumed to drift, have been widely used to assess genetic diversity in all major domestic animal species. These markers provide insight into the arrival and dispersion history of a species, with regard to their content or management history. However, no direct evidence supports current standard microsatellite markers falling under this assumption. Therefore, the objective of this study was to investigate the effect and divergence of microsatellites under different types of selection on genetic patterns and population diversity. A total of 192 birds (Gallus gallus) from eight different geographic locations were investigated using 20 microsatellites that are classified into different groups by their selective effect (neutral, positive selection, and balancing selection) by the FDIST2 outlier test. The results showed that most polymorphisms were in the balancing selection marker group, the expected heterozygosity was 0.70, the observed heterozygosity was 0.65, and the mean number of alleles was 6.91. AMOVA revealed that the balancing group contributed the lowest amount of variance among groups, which was -0.60%, the highest variance contributed within the population being 92.28% in comparison with that of other groups. A similar pattern of population genetics was revealed following Slatkin linearized F ST , principal component factor analysis, and population structure by Bayesian clustering. In conclusion, balancing selective markers offer high polymorphism for estimating genetic diversity but reduced genetic divergence between populations.

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“…We have previously reported on two cases of recombination . It may occur simultaneously at more than one locus and sometimes lead to formation of novel alleles . Recombination should be distinguished from loss of heterozygosity in which will show as an undetected antigen and this can be confirmed by typing a sample from buccal mucosa or even a peripheral blood sample when the peripheral blast count is low .…”

Section: Haplotypes Of Patient and Family Membersmentioning

confidence: 99%