"PCR Karyotype" of Monochromosomal Somatic Cell Hybrids

Following fusion of human diploid fibroblast-derived microcells with mouse A9 cells, we isolated seven monochromosomal hybrids containing a single human chromosome 2, 3, 5, 12, 15, 20, or 22. Cytogenetic analysis as well as PCR karyotyping (chromosome-specific banding pattern generated by Alu-PCR) was performed on all the hybrids. We here present, for the first time, the specific PCR karyotypes of human chromosomes 2 and 20.     

Familial translocation t(10;21)(q22;q22)

Summary A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.     

Interchange trisomy 21 by t(1;21)(p22;q22)mat

Interchange trisomy 21 by t(1:21)(p22:q22)mat: Interchange trisomy 21 by t(1;21)(p22;q22)mat was identified in a sporadic patient with Down syndrome. With a 21q22 specific probe, we observed signals on both normal 21 chromosomes and on the der. We reviewed the 23 published reports of families with reciprocal translocations leading to viable offspring with interchange trisomy 21. The breakpoints in chromosome 21 were mainly located in 21q (19/24 instances, including the present report) and in 19/23 cases the other chromosome involved in the translocation was (pairs 1-12). The underlying 3:1 segregation occurred mainly in carrier mothers; only one patient presented a de novo imbalance and in another case the father was the carrier. In addition, there were 4 instances of concurrence with another unbalanced segregation (adjacent-1 or tertiary trisomy) and 3 families with recurrence of interchange trisomy 21. The mean age of 14 female carriers at birth of interchange trisomy 21 offspring (24.8 yr) was lower that the mean (28.3 yr) found in a larger sample of mothers of unbalanced offspring due to 3:1 segregation (mostly tertiary trisomics) and was not increased with respect to the general population average. Overall, these data agree with previous estimates regarding recurrence risk (9-15%) and abortion rate (about 28%) in female carriers ascertained through an interchange trisomic 21 child.     

Recurrent abortion associated with a balanced 22;22 translocation,or isochromosome 22q in a monozygous twin

Summary A 45,XX,t(22;22)(p11;q11) or 45,XX,i(22q) chromosomal rearrangement was found in a woman with a history of recurrent abortion. A twin sister did not have the translocation even though marker studies indicate that the twins are probably monozygotic.     

A further case of a 22;22 Robertsonian translocation associated with recurrent abortions

Summary A case of 22;22 Robertsonian translocation, identified in the husband of a woman who had five early abortions, is reported.     

Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation,t(13;22)(q22;q11)

Summary A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.     

Tertiary trisomy (22q11q),47,+der(22),t(11;22)

Summary We describe a case of tertiary trisomy (22q11q) 47,XX,+der(22),(22pter22q13: : 11q2511qter) in a child with mental retardation, cleft palate, and congenital heart disease resulting from 3: 1 meiotic nondisjunction in a maternal (11;22) translocation carrier. The clinical findings in previously reported cases are reviewed and compared with the features of reported patients with partial trisomy 11q and trisomy 22 syndromes. Half of the ten reported families had additional balanced translocation carriers who may have an increased risk of having a liveborn child with an MCA/MR syndrome, although none have been reported to date.     

Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia

Although KIT mutations are present in 20–25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.     

Translocation between chromosome 7 and chromosome 22, t(7;22)(p22;q12), in a patient with chronic myelocytic leukemia

Summary A 46-year-old man with chronic myelocytic leukemia had a new variant translocation between chromosome 22 and chromosome 7 in bone marrow cells. No involvement of chromosome 9 was seen. The patient entered blastic transformation within half a year, by which time he had acquired an isochromosome 17 in addition to the variant translocation.     

Genetic mapping: Chromosomes 6–22

Using a method that considers physical assignments and the distribution of chiasmata, as well as linkage data, genetic maps are constructed for chromosomes 6, 9, 13, and 16, and unassigned markers are tested for inclusion in these linear maps.     

VID22 counteracts G-quadruplex-induced genome instability

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.     

Evaluation of "unique" aspects of human vertebral bodies and pedicles with a consideration of Australopithecus africanus

Recent functional studies of human vertebrae have revealed that loads borne by the axial skeleton during bipedal postures and locomotion pass through the pedicles and posterior elements as well as through the bodies and discs. Accordingly, particular morphological attributes of these vertebral elements have been linked exclusively with bipedalism. In order to test the validity of current form-function associations in human vertebral anatomy, this study considers the morphology of human thoracolumbar vertebral bodies and pedicles in the context of a wide comparative primate sample. The last lumbar vertebra of STS 14 (Australopithecus africanus) is also included in the analysis. Results indicate that certain features of human vertebrae previously thought to reflect bipedalism are characteristic of several nonhuman primates, including those whose posture is habitually pronograde. These features include the decrease in vertebral body surface area and the increase in cross-sectional area of the pedicle between the penultimate and last lumbar vertebra. In addition, although humans have relatively large and wide last lumbar pedicles, the enlargement and widening of the pedicle between the penultimate and last lumbar vertebra is not unique to humans. On the other hand, human vertebrae do exhibit several unique adaptations to bipedal posture and locomotion: (1) the vertebral body surface areas of the lower lumbar vertebrae and the cross-sectional areas of the last lumbar pedicles are large relative to body size, and (2) the last lumbar pedicles are wider relative to length and to body size than are those of nonhuman primates. The last lumbar vertebra of STS 14 does not exhibit any of these human-like vertebral features—its pedicles and body surface areas are relatively small, and its pedicles are not relatively wide, but relatively short.