Robert Wenk | Pennsylvania State University (original) (raw)

Papers by Robert Wenk

Transfusion, Jun 1, 2009

BACKGROUND: Almost all relationship analysts now use molecular (DNA) tests to obtain necessary ge... more BACKGROUND: Almost all relationship analysts now use molecular (DNA) tests to obtain necessary genetic information, yet older blood group tests remain valid. Circumstances may provide blood test results from old reports to avoid trying to sample DNA from inaccessible sources. CASE STUDY: A mother recently claimed that a deceased man (alleged father [AF]) sired her child. Insurance investigation recovered two paternity test reports from an AABB-accredited laboratory. The 16and 18-year-old reports employed blood groups and protein polymorphisms to exonerate two different men. One report contained the multilocus phenotypes of the AF and the other contained the phenotypes of the mother and child at the same loci. A new case was synthesized from the old reports. RESULTS: Genetic inconsistencies (three direct and one indirect) were demonstrated among the nine loci that had been typed in both the AF and the motherchild pair. CONCLUSION: New relationship tests may be reconstructed from phenotypes reported before the molecular test era. This approach avoids exhumation and other problematic methods of specimen retrieval.

Transfusion, Feb 1, 2006

BACKGROUND: The contribution of maternal typing to paternity analysis was evaluated to determine ... more BACKGROUND: The contribution of maternal typing to paternity analysis was evaluated to determine how many additional loci to study in one-parent cases. STUDY DESIGN AND METHODS: Four groups underwent paternity analyses with an eight-locus test battery. Files of 25 case trios were retrieved, in which alleged fathers had achieved paternity indices of greater than 100 ("included trios"). Maternal types were omitted and the cases were reanalyzed ("included duos"). Motherchild pairs of the cases were then coupled with unrelated men ("excluded trios"), and the cases were analyzed. Maternal types were omitted from the excluded trios and cases were reanalyzed ("excluded duos"). RESULTS: Paternity indices of men in included duos were markedly reduced when compared to included trios; odds were sufficiently low in 9 of 25 men that paternity remained in doubt. After omission of maternal phenotypes, excluded duos exposed 33 percent fewer genetic inconsistencies than excluded trios; 5 of 25 men in excluded duos demonstrated less than two genetic inconsistencies and 1 man had none. The specific probabilities of paternity exclusion in motherless cases averaged 61 percent per locus of those in case trios. One random man in 52 duos was not excluded by the eight tests versus 1 in 417 trios. CONCLUSIONS: Omission of maternal typing from eight common microsatellite paternity tests reduced conclusive evidence for or against paternity by 30 to 40 percent. False inclusion of random men is an important failing of tests in motherless cases. Cases involving one parent and child (e.g., in immigration) would require examination of an additional five similar loci to compensate for absent maternal data. A change in standards is suggested.

Transfusion, Jun 20, 2003

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Journal of craniofacial genetics and developmental biology, 1986

Study of a large five-generation kindred from southern Maryland revealed that type III dentinogen... more Study of a large five-generation kindred from southern Maryland revealed that type III dentinogenesis imperfecta (DGI-III) and a localized form of juvenile periodontitis (JP) were both segregating as autosomal-dominant traits. Linkage analyses demonstrated that these were two distinct clinical entities, making this family the first documented instance of an autosomal-dominant form of JP. Since the locus for the more common form of dentinogenesis imperfecta (DGI-II) is on chromosome 4q [Ball et al, 1982], a linkage analysis of genetic and chromosomal markers on chromosome 4 was undertaken. The results suggested that the locus for the DGI-III subtype is located a similar distance from the Gc locus (theta = 0.12) as the distance previously observed between Gc and DGI-II loci (theta = 0.11) [Ball et al, 1982; Conneally et al, 1984]. Most likely the two DGI subtypes are determined by genes at closely linked loci, by allelic genes, or by the same gene with the variable expression in diffe...

Transfusion, Nov 1, 2017

* Lowercase letters are the respective frequencies of alleles designated as uppercase letters. U ... more * Lowercase letters are the respective frequencies of alleles designated as uppercase letters. U 5 phenotype; LR 5 likelihood ratio: (probability AF transmits the locus POA) 4 (probability a RM transmits the POA).

Transfusion, Apr 9, 2012

BACKGROUND: In sibship analysis, the usual comparison of an alleged (test) sibling's short tandem... more BACKGROUND: In sibship analysis, the usual comparison of an alleged (test) sibling's short tandem repeat (STR) types with those of a reference sibling may prove inconclusive. Increasing the number of examined STR loci may not change sibship probabilities very much. We increased the number of verified reference siblings to resolve problematic cases of alleged sibship. STUDY DESIGN AND METHODS: (A) Ten paternity cases were chosen in which there were three highly probable children of each alleged father. Pairs of the alleged father's children were analyzed for full sibship. The test sib with the lowest likelihood of sibship was reanalyzed by a comparison with two reference siblings combined. (B) Five problematic sibship cases are presented to demonstrate how two-person reference pedigrees can improve diagnosis over tests using one reference person. RESULTS: (A) Two-person pedigrees exponentially increased sibship probabilities of true siblings above those produced by one reference person. (B) In problem cases, reference pedigrees provided data that: 1) statistically verified some alleged sibships in which analyses using one reference person yielded inconclusive results, 2) allowed exclusion of some alleged sibships, or 3) suggested alternate blood relationships to the alleged one. CONCLUSIONS: Use of reference pedigrees often resolves sibship questions left unsettled by tests using reference individuals. Adding reference relatives is a far more powerful analytical strategy than adding test loci. Whenever possible, verified blood relatives should be incorporated into a reference pedigree to retest an alleged sibling whose initial results were unclear.

Transfusion, Jul 20, 2004

The lower limit of residual white blood cell counting: how low is low? We were attracted by the a... more The lower limit of residual white blood cell counting: how low is low? We were attracted by the article of Burnouf and colleagues 1 who described a plasma collection technique that yields a significantly lower residual cell number than two other established procedures. The authors report white blood cell (WBC) concentrations with a lower range of 0.4 ¥ 10 4 per L (0.004 WBC/mL of plasma). We have several years of experience with flow cytometric counting of residual WBCs. With an established method based on the use of beads (TrueCount, Becton Dickinson, Franklin Lakes, NJ) as an internal standard, our lower detection limit for WBC is 0.1 per mL. In fact, for results between 0.1 and 1 WBC per mL, we estimated a practical margin of error of up to 60 percent between WBC-expected and WBC-analyzed. 2 To detect 0.1 WBC per mL, we must acquire about half of our original (100 mL) plasma sample used for WBC analysis, obtaining roughly 5 WBC events per 25,000 events acquired. The lower range reported in the article is 25 times below this. To detect 0.004 WBC per mL with any degree of precision, 2.5 mL of original sample will have to be acquired to enumerate 10 WBC events. Unfortunately, the materials and methods section does not contain the method applied to obtain the described results, and it would be extremely beneficial for us and others if the authors could provide a detailed description of their method for accurate counting of such low concentrations of WBCs. The French regulations for fresh frozen plasma require 1 ¥ 10 4 WBC per L. This value cannot be accurately determined by our own procedure (lower detection limit, 10 5 /L). We question whether this value is met by Burnouf and coworkers (mean detection, 3 ¥ 10 4 /L) and would be interested to know which practical method is proposed for accurate quantification of 1 ¥ 10 4 WBC per L plasma.

Transfusion, Sep 1, 2000

Increasingly, parentage testing laboratories are called upon to provide documentation of genetic ... more Increasingly, parentage testing laboratories are called upon to provide documentation of genetic linkage between individuals applying for legal immigration to the United States. Many embassies require that the party who has already obtained legal immigrant status document that the person(s) he or she is trying to bring into the United States is a first-degree relative, for example, establishing that the parties are parent and child. As part of this process, several embassies have started to request not only parent-child calculations, but also statistical tests for other possible relatedness, such as uncle-child or possible sibling status. In that context, Wenk and Chiafari1 demonstrate both the ways in which these indices are used and the fact that paradoxical results are often observed. Specifically, with the use of three highly informative VNTR loci, 4 of 25 examples of proven full-sibling pairs yielded a ratio of greater than 2:1 against full-sibling status. Furthermore, 2 of 25 pairs proven beyond doubt to be half-siblings had ratios exceeding 5:1 in support of full-sibling status. Because of the stringent immigration requirements, we typically test at 5 to 7 pairs of VNTR loci, which yields greater power to distinguish possible relationships. Our concern is with the ways that these indices are used by various US embassies with regard to issues of immigration. Recently, we had a case in which a married couple had legally immigrated to the United States and were trying to bring in their son. We tested the man and the boy at five highly polymorphic VNTR alleles. They (father and son) shared both alleles at three systems, and so the full-sibling index exceeded the father-child index by over 40-fold. Because of this latter calculation, the embassy refused admission of the boy to the country, despite the observation that the man was almost 40 years older than the tested child and hence far more likely to be the boy’s father than a full sibling! We subsequently tested the woman’s blood; this showed that the boy’s results were consistent with the two adults’ being his parents. It is not uncommon for genetic heterogeneity to be less diverse within a small ethnic community than in the entire classification of the race, and this gives an overrated significance to the sharing of more than a single allele. When alleles are common within a tested population, the sharing of two alleles will be correspondingly more common. This occurs even more frequently when less polymorphic systems, such as serial tandem repeats (STRs), are used. For example, alleles are more broadly distributed among all Asians than within the Japanese population alone. Hence, finding parents that share both alleles with children is not a rare event in which certain alleles are common within the tested population. In short, while we appreciate the challenges faced by embassies to follow the rules limiting immigration sponsorship to direct family members, we urge greater dialog between testing centers and the individual embassies, to establish reasonable expectations for additional testing requirements when no exclusions are found. One year after the initial testing was performed, the child in the above example remains abroad and separated from his parents. As the current system stands, families that can ill afford it are required to pay for additional testing and legal and communications costs. Jed B. Gorlin, MD Herbert F. Polesky, MD Memorial Blood Centers of Minnesota 2304 Park Avenue Minneapolis, MN 55404-3789 e-mail: jed@mbcm.org

Clinical Chemistry, Dec 1, 1969

The method describedis based on Dubowski's o-toluidine procedure for the determination of glucose... more The method describedis based on Dubowski's o-toluidine procedure for the determination of glucose in plasma, serum, or cerebrospinal fluid. It utilizes the rapidity, precision, and closed system of continuous flow analysis of an unmodified Auto-Analyzer to substantially increase sensitivity and accuracy in the low range. The method is more specific than the ferricyanide reduction method. Protein precipitation or dialysis are unnecessary except for hemolyzed specimens and only 0.042 ml of sample are required. The method is inexpensive, easily performed, and compares favorably on a practical basis with enzymatic, reducing, and other aniline dye methods.

American Journal of Clinical Pathology, Dec 1, 1970

The method described is based on Kaplan's modification of the Chaney and Marbach procedure: u... more The method described is based on Kaplan's modification of the Chaney and Marbach procedure: urea is hydrolyzed by urease to form ammonia, which is reacted with alkaline hypochlorite and phenol (Berthelot reaction). The procedure is rapid, precise, sensitive, specific, and simple. Dialysis is unnecessary and only 0.05 ml. of sample is required. An unmodified AutoAnalyzer is used; the manifold is compatible with a micromethod for glucose using o-toluidine.

Clinical Chemistry, Sep 1, 1974

An automated analyzer, in which ion-selective electrodes are used to measure sodium, potassium, a... more An automated analyzer, in which ion-selective electrodes are used to measure sodium, potassium, and chloride in serum, was assessed in a clinical sethng. Day-today precision, evaluated by replicate analysis of serum pools, yielded the following coefficients of variation for sodium, potassium, and chloride, respectively: 0.99%, 1.39%, and 0.67%. Values for chloride in both commercial control sera and aqueous standards were linearly related to concentration over a range of at least 10-220 mmol/liter; however, results with the potassium and sodium electrodes showed slight curvilinearity over the range 0-24 and 10-220 mmol/liter, respectively. Mean recoveries for sodium, potassium, and chloride for Concentrations covering the clinically important ranges were 98.3-102.3%, 95.9-100.0%, and 97.8-102.0%. The only important differences between experimental and comparison methods in sera were falsely high values obtained with the ion-selective electrode for K+ (caused by supranormal ammonia concentrations) and for Cl (caused by administered bromide). Mean sodium and chloride values obtained with the electrode did not differ significantly from values obtained by flame-emission photometry or coulometry for duplicate patients' specimens, but potassium values did differ slightly (P = .05).

Human Pathology, Nov 1, 1979

The exact pathways of urinary reflux into the renal veins were studied in four cases of clinical ... more The exact pathways of urinary reflux into the renal veins were studied in four cases of clinical obstructive uropathy and in 50 normal human cadaver kidneys. In the four clinical cases Tamm-Horsfall uromucoprotein was used as a marker for location of urine. Routine light microscopy and indirect immunofluorescence for Tamm-Horsfall uromucoprotein using rabbit antiserum showed tubular backflow up to the glomerulus. Dilated tubules filled with Tamm-Horsfall uromucoprotein ruptured into thin walled veins, forming tubulovenous anastomoses with extrusion of their contents into veins. The uromucoprotein was present in interlobar and arcuate veins with superimposed thrombosis and thrombophlebitis. Injection studies using pigmented gelatin in 45 normal cadaver kidneys and pigmented vinylite with corrosion casts in five additional kidneys complemented the clinical studies. Two types of urovascular communication were produced: the less frequent direct pyelovenous communication between a rupturing fornix and an adjacent small vein, and the more common indirect pyelovenous communication in which a ruptured fornix produced a sinus extravasate, which extended along the perivenous spaces of interlobar and arcuate veins. This extravasate gained access into the veins at points of rupture where venous tributaries joined the major veins in the renal medulla. The clinical implications of these tubulovenous and pyelovenous pathways of urinary reflux include backflow of whole urine and continued nephronic func

Transfusion, Mar 1, 1996

Background: Parentage testing laboratories may be asked to provide genetic evidence that two pers... more Background: Parentage testing laboratories may be asked to provide genetic evidence that two persons are or are not related, when no other relatives are available for study. Simple methods using autosomal, codominant, unlinked genetic systems can determine if two people are blood relatives (e.g., siblings). Study Design and Methods: The odds ratios (full sibship index) of true sibling pairs were determined from two-child paternity cases and compared with regionally and racially matched control pairs of unrelated children. The sharing of two, one, or no alleles was observed in pairs of children at three independent, polymorphic VNTR (variable number of tandem repeat) sequences loci. The sibship index was calculated as (the chance that an observation would occur if two children were siblings) divided by (the chance that it would occur if the two were unrelated). Sibship indices and the frequencies of shared alleles were determined for 20 sibling pairs and 20 control pairs. Results: Sibship index values were less than 1 in all 20 pairs of unrelated children. Sibship index values were greater than 100 in nine pairs of siblings (45%), between 10 and 100 in five pairs (25%), between 1 and 10 in four pairs (20%), and less than 1 in two pairs (10%). Siblings shared two alleles in 17 of 60 observations (28.3%); controls shared two alleles in 0 of 60 observations (0%). Conclusion: The sharing of one allele and the sharing of no alleles at a polymorphic locus of high heterozygosity provide limited information for and against sibship, respectively. The sharing of two alleles produces strong evidence favoring sibship. In a given case, the study of more than three polymorphic loci of high heterozygosity may be needed to develop the evidence that two people are siblings. The general logic and methods used for siblings apply to kinship analyses of other two-person pedigrees. Abbreviations: k coefficient = kinship coefficient; R = related; Sl(s) = sibship index (indices); U = unrelated; VNTR(s) =variable number of tandem repeat@).

Clinical Genetics, Jun 28, 2008

A new variant of blood group A [A(WAS)] was expressed in three generations of a Caucasian family:... more A new variant of blood group A [A(WAS)] was expressed in three generations of a Caucasian family: Phenotype included weak mixed field hemagglutination by anti‐A reagents, secretion of H substance, and presence of anti‐Ai in serum. The A(WAS) variant was inherited in a Mendelian fashion, dominant to O. A‐transferase activity was absent from cells and saliva but was 0.2% of normal A, transferase activity in serum, with a pH optimum of 6.0. Family members expressing A(WAS) also demonstrated partly deficient H type on cells (Hm). H‐transferase activity in serum was normal for a weak A subgroup and showed typical Km and acceptor specificities. Linkage of H‐modifier and ABO loci cannot be excluded.

American Journal of Clinical Pathology, Apr 1, 1997

Laboratory samples from two different patients produced falsepositive results. Investigations ind... more Laboratory samples from two different patients produced falsepositive results. Investigations indicated that the errors were produced by a combination of miniscule preanalytical contamination of disposables, suboptimal systems design, and very sensitive Neither universal precautions nor current guidelines for handling blood specimens address the problem of cross contamination of samples. 1,2 Two temporally related cases of false-positive results were investigated to find the source of error. In both incidents, the most likely cause was a sample-to-sample contamination by disposable transfer pipettes. This preanalytical error (a "description slip" in terms of systems analysis) may be avoided by implementing engineering controls, controlling work practices, and using physical barriers. CASE REPORTS Case 1 A hospital laboratory performed a urine screening test for drugs of abuse using an enzyme-multiplied immunoassay technique. The results were positive. When the patient vigorously denied taking drugs or any medications, a second sample was collected, analyzed, and found to be negative for drugs, whereas the original sample was again positive for the drugs. The case was investigated. Case 2 A hospital employee was accidentally injured by a needle that had been used to administer medication

Transfusion, 2018

Paternity probabilities when an alleged father is a congenital chimera * Prob. 5 probability. "X"... more Paternity probabilities when an alleged father is a congenital chimera * Prob. 5 probability. "X" 5 Prob. that child inherited the POA from the AF. If the maternal obligate allele (MOA) is identified (trios), the POA is restricted and "Y" is the POA frequency. If the mother is not tested (duos), "Y" 5 Prob. of observing the child's genotype in AF's population. LR 5 "X"/"Y." Uppercase letters are alleles. Lowercase letters are allele frequencies.

Clinical Chemistry, Mar 1, 1974

We have evaluated the performance of manually operated sampler pipets. Twenty-four instruments of... more We have evaluated the performance of manually operated sampler pipets. Twenty-four instruments of various construction, manufacture, and delivery volume were evaluated. Pipet-delivered water and serum were repeatedly weighed under controlled environmental conditions, and precision and accuracy assessed. The pipets often failed to meet the manufacturer's stated tolerance limits. Consumers should calibrate these instruments in their own laboratories. Some of the manufacturer's recommendations for optimal performance are challenged. The manual samplers can substitute for oral pipets and permit safe, inexpensive, simple, and rapid transfer of liquids, if the user recognizes their operational characteristics and limitations in accuracy and precision.

American Journal of Clinical Pathology, Mar 1, 1971

Reference methods for cholesterol, on which prediction of coronary heart disease is based, yield ... more Reference methods for cholesterol, on which prediction of coronary heart disease is based, yield values consistently lower than routine methods. Discrepancies among results obtained from different laboratories are produced by systematic bias rather than lack of intralaboratory precision. Each of 22 hospital laboratories measured the cholesterol concentrations in two common serum pools, over a month’s time, as part of a continuing regional quality control program. The mean values for each laboratory were divided by the means of a laboratory using a reference method. The ratios were applied as correction factors to assayed values of unknown serum samples. Interlaboratory differences caused by systematic bias are greatly reduced by the correction, possibly permitting transfer of accurate data among laboratories. The value and limitations of mathematic correction of systematic bias are discussed.

Archives of Pathology & Laboratory Medicine, 2003

Many perpetrators of Munchausen syndrome by proxy present bloodstained materials as counterfeit e... more Many perpetrators of Munchausen syndrome by proxy present bloodstained materials as counterfeit evidence of proxy hemorrhage. Although blood grouping may show that the blood is not the proxy's, DNA typing may specifically identify the blood's source. A mother claimed that she alone had witnessed gastrointestinal bleeding of her son and presented bloodstained towels as evidence. Several clinical investigations had failed to reveal a bleeding source. I compared the DNA types of the bloodstains and the child's buccal cells. The bloodstain and epithelial cells differed at 4 of 8 microsatellite loci and at the amelogenin locus. The blood and buccal cells shared 1 allele at every locus, suggesting that their sources were closely related. The probability that the source of the blood was maternal was 0.9915 (prior probability, 0.5). I recommend DNA matching in suspected cases of Munchausen syndrome by proxy whenever blood is presented as evidence.