Herman E. Wyandt

Texas Tech University Health Sciences Center, Lubbock, Texas, United States

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Publications (58)198.96 Total impact

  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: An initial attempt to assess the frequency of variants was made in non-banded chromosomes from consecutive newborns by Lubs and Ruddle (Science 169:495–497, 1970). Their study included 3,476 infants of white mothers and 807 infants of black mothers, all of whom were phenotypically normal except one child with low birth weight. A total of 2,131 variants involving chromosomes A1, C9, E16, the short arms and satellites of D and G group chromosomes, and Y long arm were scored. Frequencies of certain striking variants were found to be discrepant between black and white children (Table 3.1). In particular, a metacentric C9 variant (later recognized as a 9qh inversion) was 20 times more frequent in the black children; a large short arm on a D-group chromosome was four times more frequent. Y chromosome length was not different for black and white children. However, a large Y (> E18) was present in one of nine Chinese infants included in the study and a second large Y was present in the only Turkish infant. Earlier studies had shown a high frequency of large Y in Japanese adult males (Lubs and Ruddle, Nature 233:134–136, 1971).
    Human Chromosome Variation: Heteromorphism and Polymorphism, 01/2011: pages 33-42; , ISBN: 978-94-007-0895-2
  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: The lightly-stained secondary constriction of chromosome 9 by plain Giemsa distinguishes it from other C-group chromosomes (Patau et al., Lancet i:790–793, 1960; Ferguson-Smith et al., Cytogenetics 1:325–343, 1962; Palmer and Funderburk, Cytogenetics 4:261–276, 1965). By G-banding, the secondary constriction itself stains lightly, but bands on either side of the centromere typically stain as intensely as the pericentromeric regions of other chromosomes (Fig. 14.1a–i). By C-banding or DA/DAPI staining, the entire region, including the pericentromeric bands usually consists of a uniform block of dark or brightly staining heterochromatin (Fig. 14.1m, n). Sometimes, however, blocks of heterochromatin will appear to be separated by a G-positive, C-negative band (Fig. 14.1j, k). More rarely, such C-negative bands can be quite striking and have been the object of considerable study (see Euchromatic Variants). The 9qh region is also strikingly stained by Giemsa-11 (Fig. 2.4) (Bobrow et al., Nature New Biol 238:122–124, 1972; Wyandt et al., Exp Cell Res 102:85–94, 1976).
    Human Chromosome Variation: Heteromorphism and Polymorphism, 01/2011: pages 131-134; , ISBN: 978-94-007-0895-2
  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: Persistent notions that striking chromosomal heteromorphisms are directly associated with clinical anomalies or have some indirect effect on the frequencies of major chromosome abnormalities or spontaneous miscarriages, have been the topics of numerous studies. Early studies (Lubs et al., Population cytogenetic studies in humans, pp. 133–159, 1977; Tharapel and Summitt, Hum Genet 41:121–130, 1978; Funderburk et al., Am J Med Genet 1:301–308, 1978; Matsuura et al., Hum Genet 523:203–210, 1979) suggested roles of striking variants in mental retardation, autism, behavior disorders and congenital anomalies. In general, such studies were small and most were not substantiated. Soudek and Sroka (Clin Genet 16:109–116, 1979) gave four attributes of heteromorphisms: (1) they contained repetitive satellite DNA; (2) they were inherited; (3) there were no syndromes associated; and, (4) if phenotypic effects were associated, they were most likely due to an indirect selective effect. Barlow (Hum Genet 17:105–136, 1973) suggested that extra heterochromatin might affect birth weight, body weight, immunoglobulin levels and cell growth. He also pointed out the difficulties technical variables make in comparing different studies. Similar points were made by Maes et al. (J Med Genet 20:350–356, 1983). Generally, there was no definitive evidence for a direct role of variations in size of the common heteromorphisms on phenotype or in mental retardation.
    Human Chromosome Variation: Heteromorphism and Polymorphism, 01/2011: pages 43-50; , ISBN: 978-94-007-0895-2
  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: The term heteromorphism is especially applicable to normal variants observed by chromosome banding techniques. However, normal variations in morphology in certain regions of the human genome were noted even before the advent of chromosome banding. In the first Conference on Standardization in Human Cytogenetics in Denver in 1960 (Denver Conference, Lancet 1:1063–1065, 1960/1966), chromosomes were divided into Groups A-G based on their relative sizes and positions of the centromeres. The X chromosome fell somewhere in the C-group. The Y was distinguishable from the G-group by its lack of satellites and somewhat distinctive morphology. At the London Conference in 1963 (London Conference Cytogenetics, 2:264–268, 1963), prominent secondary constrictions were identified near the centromeres in the no. 1 chromosome pair in the A- group, in a chromosome pair (no. 9) in the C-group and in a pair (no. 16) in the E-group. By the Chicago Conference in 1966 (Chicago Conference, The National Foundation, New York, 1966), it was generally recognized that these regions and the Y varied in length, and that there were morphological variations in the short arms of the D- and G-group chromosomes.
    Human Chromosome Variation: Heteromorphism and Polymorphism, 01/2011: pages 7-32; , ISBN: 978-94-007-0895-2
  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: According to Sutherland and Hecht (Giraud et al., Hum Genet 34:125–136, 1976), fragility at specific sites on chromosomes were first described by Dekeban (1965) and by Lejeune (1968). Magenis et al. (1970) (Harvey et al., J Med Genet 20:280–285, 1977) used a heritable fragile site on chromosome 16 to map α-haptoglobin. The term “fragile site”, however, is attributed to Frederick Hecht who, in referring to this site on chromosome 16, “wanted to convey the concept of transmissible points of chromosome fragility in the human genome” (Giraud et al., Hum Genet 34:125–136, 1976). The clinically significant fragile site at Xq27.3 was initially reported by Lubs (Lubs, Am J Hum Genet 21:231–244, 1969) as a familial marker X chromosome in four mentally retarded males and their normal mother. This marker was shown to be more than sporadically associated with a common form of X-linked male mental retardation in 1976–77 (Sutherland, Science 197:265–266, 1977; Sutherland, Am J Hum Genet 31:125–135, 1979). However, it was not until Sutherland (Hecht and Sutherland, Fragile Sites on Human Chromosomes, 1985) showed that expression of the fragile X required culture in medium that was deficient in folic acid and thymidine that the fragile X in particular was accepted as a reproducible marker of the disease, and that other fragile sites became of interest as possible markers of disease. It was soon apparent that numerous other sites were sensitive to a variety of culture conditions (Giraud et al., Hum Genet 34:125–136, 1976). These included: (1) folate-sensitive sites; (2) distamycin A-inducible sites; (3) BrdU–requiring sites; (4) common fragile sites (most strongly induced by aphidicolin, but weakly induced by conditions in the first three groups).
    Human Chromosome Variation: Heteromorphism and Polymorphism, 01/2011: pages 179-193; , ISBN: 978-94-007-0895-2
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    ABSTRACT: A 10-year-old African-American male has been followed since 2 years of age due to his mental retardation, severe behavioral problems, and dysmorphism. Conventional cytogenetic analysis, chromosome painting, high-resolution comparative genomic hybridization (HR-CGH), and bacterial artificial chromosome fluorescent in situ hybridization (BAC FISH) revealed an apparent duplication in the short arm of a chromosome 11, dup(11)(p14.3p15.1), seen also in his mentally retarded mother. The proband had moderate to severe mental retardation, a history of IUGR, infantile hypotonia, FTT, exotropia, inguinal hernia repair, and several dysmorphic features. His mother had mild mental retardation, a history of impulsivity, assaultive outbursts, and similar dysmorphism. Although G-banding and FISH indicated a duplication, HR-CGH confined the localization of material to bands 11p14-11p15 and aided the selection of locus-specific BAC clones to more precisely characterize the duplicated region. To our knowledge, the results represent the first example of a familial, cytogenetically visible duplication of euchromatin in 11p that excludes the Beckwith-Wiedemann syndrome critical region. It is possible that one or more genes had been disrupted at the breakpoints of the above structural chromosomal rearrangement giving rise to the present phenotype.
    Experimental and Molecular Pathology 07/2006; 80(3):262-6. DOI:10.1016/j.yexmp.2005.12.008 · 2.71 Impact Factor
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    ABSTRACT: A newborn female presented with costovertebral dysplasia (CVD), subtle facial anomalies, and neonatal respiratory distress. Her karyotype demonstrated a small supernumerary NOR-positive marker that was subsequently identified as del(22)(q11.2). This extra structurally abnormal chromosome was found by DNA microsatellite marker analyses to be derived from a paternal chromosome 22. The child has had severe growth and developmental delay along with pulmonary insufficiency and hypoxia but is presently stable at age 20 months. Findings in our patient correlate with similar observations in children with small markers derived from D/G and D/D translocations reported before banding technology was available. These reports and recent mapping results suggest that a pericentric gene family, distributed on one or more acrocentric chromosomes, may have played a role in the development of the human axial skeleton. Data from additional studies will be needed to confirm or refute this hypothesis.
    Experimental and Molecular Pathology 05/2006; 80(2):197-200. DOI:10.1016/j.yexmp.2005.08.011 · 2.71 Impact Factor
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    ABSTRACT: Rapid fluorescence in situ hybridization (FISH) performed on 1,788 amniocenteses, using Aneuvision (Vysis) probes for chromosomes 13, 18, 21, X, and Y, over several years, yielded 115 cases with percentages of aneuploidy between 4 and 100%. All cases above 60% were confirmed to be positive by chromosome analysis. Fifteen of forty-one cases that would be considered inconclusive by generally accepted criteria (i.e. with less than 60% of cells with an abnormal signal pattern) revealed lower cutoffs to be positive when confirmed by chromosome analysis. For trisomy 21, 6 cases with percentages from 36 to 57% were positive; 4 of 7 cases with percentages from 22.5 to 33% were positive; 11 cases with percentages of 13% or less were negative. Similar trends were found for aneuploidies of 13, 18, X, and Y. However, the number of abnormal cases is still too small to determine definitive cutoffs in the <60% gray zone. An average of 57 metaphases was analyzed for cases with FISH percentages below 60%. Despite the wide range of abnormal FISH percentages for chromosomally positive cases, we found no examples of autosomal mosaicism in this series. Although sex chromosome mosaicism was cytogenetically evident in several cases, there was little direct correlation between cytogenetic and rapid FISH results. FISH results involving sex chromosomes were more frequently confounded by maternal cell contamination and other technical factors.
    Fetal Diagnosis and Therapy 02/2006; 21(2):235-40. DOI:10.1159/000089310 · 2.94 Impact Factor
  • Herman E. Wyandt · Vijay S. Tonk · Xinli Huang
    Fetal Diagnosis and Therapy 01/2006; · 2.94 Impact Factor
  • Herman E. Wyandt · Sung Han Shim · Xinli Huang · Jeff M. Milunsky
    Experimental and Molecular Pathology 01/2006; · 2.71 Impact Factor
  • Hon Fong L Mark · Herman Wyandt · Agen Pan · Jeff M Milunsky
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    ABSTRACT: We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous Wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of Wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1.
    Cancer Genetics and Cytogenetics 11/2005; 162(2):166-71. DOI:10.1016/j.cancergencyto.2005.05.012 · 1.93 Impact Factor
  • H F L Mark · H Wyandt · X L Huang · J M Milunsky
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    ABSTRACT: We describe the structure of a supernumerary marker in a child who presented with a right atretic ear and multiple congenital anomalies. Using G-banding, fluorescent in situ hybridization (FISH), P1 artificial chromosome FISH and high-resolution comparative genomic hybridization (CGH), the marker was demonstrated to be a derivative chromosome resulting from malsegregation of a paternal 8;22 translocation: 47,XY, +der(22)t(8;22)(q24.1; q11.2). This case is noteworthy because the marker, while sharing similarities to der(22) in the Cat Eye syndrome (CES), also contains chromosome 8q material. This partial 8q trisomy confounds the diagnosis of CES associated with pure trisomy or pure tetrasomy 22q. The paternal translocation is noted with prolonged infertility and oligospermia, which again highlights the utility and necessity of chromosome analysis in this setting.
    Clinical Genetics 09/2005; 68(2):146-51. DOI:10.1111/j.1399-0004.2005.00466.x · 3.93 Impact Factor
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    ABSTRACT: At 6 years of age, a boy with bilateral sensorineural deafness, lateral displacement of inner canthi, a bulbous nasal tip, synophrys, and cryptorchidism was clinically diagnosed as having Waardenburg's syndrome type I (WS-1). In addition, he had a lumbar spina bifida with hydrocephalus shunted on the second day of life and severe mental retardation with a head circumference at the fifth percentile. Neither parent showed signs of WS-1, and the family history was negative. Because of the WS-1 features, attention was focused on the PAX3 location in 2q, at which time a de novo paracentric inversion of 2q23-q37.1 was noted. Subsequent high-resolution chromosome analysis 8 years later indicated a complex rearrangement involving regions 2q31-q35 and 2q13-q21. Whole chromosome painting and high-resolution comparative genomic hybridization yielded negative results for any translocation, duplication, or deletion of any chromosome segments. Sequencing of the PAX3 gene yielded no detectable mutation. Fluorescent in situ hybridization (FISH) studies with human BAC clones revealed five breakpoints in chromosome 2q resulting in two paracentric inversions and one insertion, the karyotype being interpreted as 46,XY,der(2)inv(2)(q13q21)inv(2)(q21q24.2)ins(2)(q24.2q33q35). In this extremely rare chromosomal rearrangement, the FISH result showed a breakpoint at 2q35 being proximal to and without involvement of the PAX3 gene. While further studies continue, possible interpretations include involvement of a regulatory gene(s) for PAX 3 and other genes at the other breakpoints related causally to the spina bifida and mental retardation.
    Clinical Genetics 08/2004; 66(1):46-52. DOI:10.1111/j.0009-9163.2004.00276.x · 3.93 Impact Factor
  • Herman Wyandt · Vijay Tonk
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    ABSTRACT: Fluorescence in-situ hybridization (FISH) is the latest technology for studying specific sequences on whole chromosomes. Discussing all ramifications and applications is beyond the scope of this book. However, FISH methodologies hold unlimited promise as a means to more accurately identify and characterize chromosomal variants. In principle, any piece of DNA can be cloned, sequenced, characterized, amplified, labeled and hybridized to intact chromosomes or nuclei and detected. These cloned DNA segments, called probes, are prepared by a variety of techniques including: (1) synthesis of cDNAs from mRNAs by reverse transcriptase [1]; (2) isolation of specific sequences by PCR amplification and/or gel electrophoresis [2,3]; (3) propagation of larger DNA fragments in bacteria or yeast by insertion into cloning vectors such as plasmids, phage, cosmids, BACS, or YACS [4,5]; (4) isolation and cloning of partial or complete DNA libraries from specific chromosome regions or entire chromosomes by microdissection [6,7] or chromosome sorting [8,9]. Whatever the source, labeling is usually completed by nick translation or random priming with nucleotides that either have fluorescent label attached directly or combined with a ligand that is recognized by a fluorescent-tagged protein [10,11].
    Atlas of Human Chromosome Heteromorphisms, 01/2004: pages 87-95; , ISBN: 978-90-481-6296-3
  • Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: The first major population studies of human chromosomes were an eventual collaborative effort with data collected from 56 952 newborns from six different countries [1–7]. These, for the larger part, were initiated on unbanded chromosome material and in most centers were based on examination of two to five metaphases from each subject. The frequency of major chromosome abnormalities from these studies forms the basis of much of the statistical knowledge relating to frequencies of the major chromosome abnormalities, both numerical and structural. In tabulations of the results of these studies [8], however, there was a conscious effort to exclude normal morphological variants. The rationale for this was that, even though variants of certain chromosomes were well known, chromosome banding techniques were discovered before most of these studies were completed, so that it was quickly realized that accurate determination of variants in the majority of chromosomes was not possible in non-banded material. Nevertheless, a specific attempt to assess variants in unbanded chromosomes from 4482 consecutive newborns was made by Lubs and Ruddle [9] in New Haven, Connecticut. Their study included 3476 infants of White mothers and 807 infants of Black mothers. All of the children were phenotypically normal except for one White child with low birth weight. Criteria for the most common variants were established for chromosomes A1, C9, E16, the short arms and satellites of D and G group chromosomes, and Y long arm. A total of 2131 variants were scored.
    Atlas of Human Chromosome Heteromorphisms, 01/2004: pages 33-46; , ISBN: 978-90-481-6296-3
  • Shivanand R. Patil · Herman E. Wyandt
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    ABSTRACT: Several early studies suggested that variations in size of heterochromatic (C-banded) regions on human chromosomes might have deleterious effects [1–5]. In particular, studies by Lubs et al. [4,5] suggested an increased frequency of 9qh+ in retarded Black males. Tharapel and Summitt [6] studied 200 mentally retarded children and 200 normal adults by G-, Q- and C-banding techniques. They found an increased frequency of 9qh+ in Black but not in White subjects. No significant differences were seen for prominent or decreased size of short arms satellites of acrocentrics, 1qh, 9qh, 17ph, 17qh or for inversions of 9qh. Funderburk et al. [7] examined the frequency of minor variants in 1289 child psychiatric subjects with moderate retardation, autism or chronic behavior disorders. One-fourth had behavior problems and three-fourths had congenital abnormalities and severe mental retardation. Overall, they found an increased frequency of 9qh+. However, they also found only a random association with prominent qh regions, prominent satellites or long Y, although racial differences were evident as had been shown earlier. Matsuura et al. [8] studied Q-band heteromorphisms in 374 mentally retarded individuals from a variety of ethnic backgrounds, including Oriental, Filipino, Caucasian and Polynesian. Although differences were seen for 3cen, 13p and 14p, except for the size of the Y chromosome, none of these differences among the races was significant. 13cen and 13p 11 were larger in a group with socio-familial retardation, significant at the 0.05 level, but because of the small size of the various groups, the observation was not considered to be important.
    Atlas of Human Chromosome Heteromorphisms, 01/2004: pages 47-62; , ISBN: 978-90-481-6296-3
  • Chapter: Plates
    Herman E. Wyandt · Vijay S. Tonk
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    ABSTRACT: The following plates represent examples of human chromosome heteromorphisms that have been contributed by individual investigators specifically for this volume, by us or have been reprinted with permission from various published sources. Individual contributions have been identified by a numerical designation prefixed with the letter “c,” after the name of the contributor, i.e. Lauren Jenkins (c2). A complete alphabetical listing of contributors, their titles, and affiliations is given in the List of Contributors at the front of Part I, followed by c2, c6, etc. to indicate the number(s) of their contribution(s).
    Atlas of Human Chromosome Heteromorphisms, 01/2004: pages 127-273; , ISBN: 978-90-481-6296-3
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    ABSTRACT: We present our experience with cross-hybridization of D15Z1, used in combination with D15S10, D15S11 or SNRPN, in 109 clinical cases referred for Angelman syndrome (AS), Prader-Willi syndrome (PWS), for autism to rule out duplication of 15q11.2, or to identify structural chromosome abnormalities thought to involve chromosome 15. Nine cases with normal karyotypes studied with at least one of these probe mixtures showed an extra signal with D15Z1 on a chromosome 14. One case showed absence of the D15Z1 signal from 15p and one case showed an extra signal with D15Z1 on both chromosome 14s. Sixteen cases from this series had structural abnormalities, which included ten cases with supernumerary markers, three of which had a D15Z1 signal on a chromosome 14. The remaining cases did not have an extra signal on chromosome 14, but included rearrangements between Y and 15, 15 and 19, and a r(15), all with breakpoints in 15p11.1 or p11.2. Of the three cases with a supernumerary marker and an extra D15Z1 signal on a chromosome 14, one was a maternally derived marker, while the variant 14 was paternal in origin. The other two markers were de novo. The high frequency of variant 14 in cases with supernumerary markers (30%) was not significant by Chi-square analysis compared to the overall frequency in 109 cases of 11.9%. The overall frequency is consistent with a previous report by Stergianou et al. (1993). We can now add that a false-negative result may occur slightly less than 1% of the time. The chance that both chromosome 14 homologs will be positive for D15Z1 is theoretically about 1 in 300. If associated with an abnormal phenotype, the possibility of uniparental disomy should be ruled out.
    Journal of the Association of Genetic Technologists 02/2003; 29(4):146-151.
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    ABSTRACT: Disease associated balanced chromosome rearrangements (DBCR) causing truncation, deletion, inactivation or over-expression of specific genes are instrumental in identifying and cloning several disease genes and are estimated to be much more common than anticipated. In one survey, the minimal frequency of combined balanced de novo reciprocal translocations and inversions causing abnormal phenotype is estimated to be 0.17%, a sixfold increase compared to the general population suggesting a causative linkage between the abnormality and the observed phenotypic traits. Here, we report two new cases of apparently balanced de novo translocations resulting in developmental delay and dysmorphic features.
    Annales de Génétique 01/2003; 46(1):37-43. DOI:10.1016/S0003-3995(03)00005-4
  • X-L.Huang · HE.Wyandt · JM. Milunsky

Publication Stats

678 Citations
198.96 Total Impact Points


  • 2006
    • Texas Tech University Health Sciences Center
      • Department of Pediatrics
      Lubbock, Texas, United States
  • 1991–2005
    • Boston University
      • • Department of Medicine
      • • Center for Human Genetics
      Boston, Massachusetts, United States
  • 1989–2004
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1989–2001
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1990
    • Tufts Medical Center
      • Department of Pediatrics
      Boston, Massachusetts, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Boston Medical Center
      Boston, Massachusetts, United States
    • Center for Human Genetics, Inc.
      Cambridge, Massachusetts, United States