Small Supernumerary Chromosomes Research Articles

Molecular Cytogenetic Characterization of Chromosome Markers

The clinical significance of marker chromosome depends on the origin of the marker, size and presence of euchromatin. We report the results of fluorescence “in situ” hybridization (FISH) studies on ten marker chromosomes. Six of these markers were derived from chromosome 15 and ranged in size from a small bi-satellite supernumerary marker to a large isodicentric inverted duplication including the euchromatic region 15q11-q13. This large marker was found in a 25-year-old severely mentally retarded male with oval face, seizures and abnormal speech and gait. Two of the medium size inv dup(15) were detected prenatally. These markers had a small euchromatic region labeled with the whole chromosome 15 probe and no signal for GABR3 and SNRPN of the 15q11-q13 region. Two chromosome 18 markers were analyzed and one of them was an isochromosome 18p labeled with 18p specific probe. The other two markers were derived from chromosome 13. One was a small centromeric supernumerary chromosome, the other was a small metacentric chromosome with two signals for the 13q32-q33 region and for the telomeric probe 13q34→qter and no signal for any alpha satellite centromere. Thus, this isodicentric 13q marker had a functional neo-centromere. The patient was a mosaic with one and two extra markers causing tetrasomy and polysomy 13q32→qter and clinical features of trisomy 13q3.

Mosaicism for a small supernumerary chromosome 22 associated with dysmorphic features and early onset dementia

A 46 -year old female was referred to the neurologist by her optometrist for a right homonymous superior field defect. As an infant, she was diagnosed as having multiple congenital abnormalities that included micrognathia which required several jaw surgeries, multiple ear tags as well as problems with rectal weakness which required surgery. She also indicated that for a couple of years she has been experiencing poor memory. On physical examination, she was noted to have a long narrow face with downward slanting palpebral fissures, a small jaw and mild scoliosis. Her mental status was within normal limits to language, comprehension and repetition.Neuropsychology testing revealed impaired psychomotor ability, reduced executive functioning and border- line visual memory. A neuro-ophthalmologist confirmed the diagnosis of right homonymous superior quadranopsia probably due to a congenially smaller or dysplastic left occipital lobe. A SPECT scan showed decreased activity in the right temporal and bilateral superior parietal lobes consistent for the early stages of Alzheimer's disease.Peripheral blood chromosome analysis revealed a mosaic karyotype, 47,XX+mar[3]/46,XX[17]. The marker chromosome was identified using whole chromosome paint probes and FISH analysis to be derived from chromosome 22. Some of the phenotypic features seen in this patient are similar to that of the Cat-eye syndrome which also has a supernumerary chromosome derived from chromosome 22. In addition, our patient seems to have symptoms of early onset dementia. It is not clear whether this is associated with the marker chromosome 22.

Unusual features in children with inv dup(15) supernumerary marker: a study of genotype-phenotype correlation in Taiwan.

Recent molecular cytogenetic studies have elucidated the origin and nature of extra structurally abnormal chromosomes (ESACs) or small supernumerary chromosomes, which are often associated with developmental delay and malformations. We studied the prevalence of inv dup(15) in a nationwide screening programme for mentally retarded children in Taiwan and tried to correlate the genotype and phenotype in those patients. Fluorescence in situ hybridization (FISH) analysis using D15Z, D15Z1, and the cosmids from the Prader-Willi/Angelman syndrome chromosome region (PW/ASCR) was performed on 54 patients (0.45%) with ESACs from 11893 probands within a 5-year period. Of them, inv dup(15) was confirmed in 25 children (46.3%) by FISH analysis. The PW/ASCR probes were used to clarify the size and DNA composition of the markers. Patients with inv dup(15) chromosomes, containing only the heterochromatin or little euchromatin of the proximal 15q (i.e., pter-->q11:q11-->pter) may have a rather mild or nearly normal phenotype (group 1). Only one patient had some features suggestive of Angelman syndrome, but was considered to be a result of deleted (15)(q12) in the chromosome 15 homologue. Additional copies within D15S11 through GABRB3 (15q11.2-13) resulted in an abnormal phenotype which involved mental and developmental delay but was different from the classical phenotype of PW/AS (groups 2, 3). Signs of autistic behavior did occur in each group. FISH combined with microsatellite analyses showed that the marker was often of maternal origin in de novo cases (n = 12, 86%), or inherited from the mother in only one familial case. Down-inv dup(15) was mentioned in two cases. Unusual features including diaphragmatic eventration, hyperlaxity of joints, arachnodactyly, brain atrophy, epilepsy (particularly infantile spasm), ataxia, genital abnormalities, and cleft lip/palate were noted in those patients. This observation expands the range of phenotypic expression associated with this relatively common ESAC. Marked phenotypic diversities exist in children with inv dup(15), dependent upon the size or genetic composition of the markers, degree of mosaicism, parental origin and familial occurrence or not. Patients with a larger inv dup(15) marker chromosome including the PW/ASCR may have a higher risk of abnormalities, but not the typical Prade-Willi/Angelman syndrome phenotype.

Synapsis in supernumerary chromosomes of Prochilodus lineatus (Teleostei: Prochilodontidae)

Summary Meiotic analysis performed on a sample of 10 specimens of Prochilodus lineatus revealed continuous filaments of different sizes stained by AgNO3, corresponding to the bivalent of the normal complement. Small supernumerary chromosomes were observed as isolated and well stained bodies, scattered among the other elements. Synaptonemal complex studies have shown that the beginning of chromosome pairing process in P. lineatus usually occurs from the telomeres to the pericentromeric region. At the end of the pachytene 27 bivalents are perfectly paired and the small supernumerary chromosomes of this species are seen as bivalents, trivalents, or tetravalents. The central region of these small chromosomes show a trick staining when they formed bivalents or tetravalents. This portion seems to correspond to the pericentromeric region of the regular chromosomes with the heterochromatic characteristic of B chromosomes.

Supernumerary ring chromosome 17 identified by fluorescent in situ hybridization

We present a patient with multiple anomalies and severe developmental delay. A small supernumerary ring chromosome was found in 40% of her lymphocyte cells at birth. The origin of the marker chromosome could not be determined by GTG banding, but fluorescent in situ hybridization (FISH) later identified the marker as deriving from chromosome 17.

C-band Polymorphism in Paris tetraphylla Chromosomes in Four Populations of Kumamoto Prefecture.

The C-band polymorphism of chromosomes in Paris tetraphylla (2n = 2x = 10) was confirmed in the plants from the four populations, i.e., Miike (Mi), Kunimi (Kn), Kikuchi (Kk) and Aso (As), in Kumamoto Prefecture of Kyushu. The five chromosomes, A, B, C, D and E, constituting a genomic set were polymorphic for the C-banded patterns, respectively. The number of different types due to the patterns of C-banded chromosomes was 5 in each of chromosomes A, B and E, 3 in C, and 4 in D. In addition, small telocentric supernumerary chromosome was C-banding positive in its entire arm.The patterns of occurrence of various types of chromosomes A to E were more or less similar between Mi and Kn populations, there being similar environmental conditions, including vegetation. On the other hand, Kk and As populations were different from the other populations in the patterns of occurrence of various chromosome types and in their environmental conditions including vegetation. Therefore, it might be considered that different chromosome types due to the patterns of C-bands distribute according to the adaptability to environmental conditions including vegetation among the populations. This speculation might be supported by the occurrence of supernumerary chromosomes in both Kn and As populations but absence in both Mi and Kk population.

Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization

Extra structurally abnormal chromosomes (ESACs) are small supernumerary chromosomes often associated with developmental abnormalities and malformations. We present 50 probands with ESACs characterized by fluorescence in situ hybridization using centromere-specific probes and chromosome-specific libraries. ESAC-specific libraries were constructed by flow sorting and subsequent amplification by DOP-PCR. Using such ESAC-specific libraries we were able to outline the chromosome regions involved. Twenty-three of the 50 ESACs were inverted duplications of chromosome 15 [inv dup(15)], including patients with normal phenotypes and others with similar clinical symptoms. These 2 groups differed in size and shape of the inv dup(15). Patients with a large inv dup(15), which included the Prader-Willi region, had a high risk of abnormality, whereas patients with a small inv dup(15), not including the Prader-Willi region, were normal. ESACs derived from chromosomes 13 or 21 appeared to have a low risk of abnormality, while one out of 3 patients with an ESAC derived from chromosome 14 had discrete symptoms. One out of 3 patients with an ESAC derived from chromosome 22 had severe anomalies, corresponding to some of the manifestations of the cat eye syndrome. Small extra ring chromosomes of autosomal origin and ESACs identified as i(12p) or i(18p) were all associated with a high risk of abnormality.

Complete characterization of a large marker chromosome by reverse and forward chromosome painting.

Marker chromosome are small supernumerary chromosomes that are sometimes associated with developmental abnormalities. Hence, the genes involved in such cases provide an interesting approach to understanding developmental abnormalities in man. As a first step towards isolating such sequences, marker chromosomes need complete characterization. By combining chromosome isolation by flow sorting and the "degenerate oligonucleotide primed - polymerase chain reaction", we have constructed a DNA library specific for a marker chromosome found in a child with severe developmental abnormalities. We used fluorescent in situ hybridization of the library onto normal metaphase spreads ("reverse chromosome painting") and were thus able to determine that the marker consists of the centromeric part of chromosome 7, the telomeric region of the long arm of chromosome 5 and the telomeric region of the short arm of the X-chromosome. Subsequently, we hybridized normal chromosome-specific libraries of the relevant chromosomes onto metaphases containing the marker chromosome ("forward chromosome painting") and could in this manner establish the precise location of the different chromosome regions on the marker chromosome itself. This is a general approach suitable for outlining marker chromosomes in detail, and will aid the identification of the genes involved.

Complementary duplication and deletion of 17 (pcen----p11.2): a family with a supernumerary chromosome comprised of an interstitially deleted segment.

A sister and brother were investigated because both were developmentally delayed although they had somewhat different physical anomalies. The girl was found to have an interstitial deletion of chromosome 17. Her karyotype was 46,XX,del(17) (pter----p11.2::cen----qter). Her brother had normal chromosomes in peripheral lymphocytes. Cytogenetic investigation of the mother showed the presence of the same deletion as in her daughter and a small supernumerary chromosome. The supernumerary chromosome appeared to contain the material deleted from the short arm of 17 since the mother's phenotype was normal. Study of skin fibroblasts in her son showed that he was mosaic for a normal cell line and one that contained the extra small chromosome; thus, he had mosaic partial trisomy 17(cen----p11.2). The origin of the centromere and telomere(s) of the small supernumerary chromosome in this family presents an interesting problem.

Formation of a minichromosome by excision of the proximal region of 17q in a patient with von Recklinghausen neurofibromatosis

An interstitial deletion, 17cen----q11.2 (or q12), and a small extra chromosome was found in a sporadic case of von Recklinghausen neurofibromatosis (NF1). In situ hybridization with a chromosome 17-specific alpha-satellite probe showed that the small chromosome was derived from the deleted region, most likely by an excision/ring formation. This chromosome rearrangement is in agreement with the localization of the von Recklinghausen neurofibromatosis (NF1) locus to the proximal region of 17q, but with a more distal breakpoint than observed in two previously described reciprocal translocations associated with NF1. If the NF1 gene has been truncated by the present rearrangement, it may suggest that the NF1 gene is a very large gene at the genomic level. Alternatively, NF1 in this patient may be caused by the gradual loss in somatic cells of the small chromosome carrying an intact NF1 gene, thereby suggesting a recessive mechanism at the gene level. Finally, an intact NF1 gene may have been placed in close proximity with alpha-satellite sequences, which might cause inactivation of the gene. The small supernumerary chromosome may not only facilitate the cloning of the NF1 gene itself, but also offers explanations of the mechanism underlying development of the disease.

Nucleolar activity of B-chromosomes inAllium cernuum (Alliaceae)

Nucleolar activity was analyzed in two samples of plants of the wild onion speciesAllium cernuum, one from Canada (2n=14) and one from the United States of America (2n=14+3B), using phase contrast analysis and C- and Ag-NOR-banding. Three chromosome pairs of the standard A-chromosome complement show small telomeric satellites, which corresponds to the maximum number of Ag-NOR-bands at metaphase and to the telomeric C-heterochromatin. However, the maximum number of nucleoli observed at interphase was eight, indicating that another chromosome pair possesses nucleolar activity. Corresponding results were obtained for the A-chromosome complement of plants from the United States of America, however, these plants further possess three small metacentric supernumerary chromosomes, which show telomeric satellites on both arms, corresponding to two telomeric Ag-NOR-bands observed after silver staining. The presented data clearly indicate that the B-chromosomes ofAllium cernuum possess rDNA gene clusters which show strong nucleolar activity.

Unusual germ line limited chromosomes in Acricotopus lucidus (Diptera, Chironomidae)

A small supernumerary polytene chromosome was found during the last 8 years in some rare cases in larval salivary gland cells of Acricotopus lucidus (Diptera, Chironomidae). The chromosome may be derived from the germ line restricted parts of the genome. It consists of a short heterochromatic segment and of euchromatic sections with banding patterns homologous to sections of the short arm of soma chromosome I. When examining male meiosis, an exceptional small germ line limited chromosome was found. It is believed that this chromosome was not always recognized during soma elimination as a germ line limited chromosome, probably because of its partial homology to one of the soma chromosomes, and was then polytenized in salivary gland cells. Another germ line limited chromosome with a characteristic morphology and with a special behavior in differential gonial mitosis was found to have existed for more than 12 years in a laboratory stock. In differential gonial mitosis this special germ line limited chromosome partly pairs with the long arm of soma chromosome I. The present results strongly support the idea that the germ line limited chromosomes of A. lucidus are derived from the soma chromosomes, and show that chromosomes of the germ line restricted part of the genome can persist for many generations in a laboratory stock in spite of complex chromosome elimination mechanisms in the primary germ cells. Key words: germ line limited chromosomes, supernumerary polytene chromosome, salivary gland, Acricotopus lucidus.

DNA probe localization at 18p113 band by in situ hybridization and identification of a small supernumerary chromosome.

Recombinant plasmid clone B74 (also named D18 S3) containing a human single-copy DNA segment of 6 kilobases (kb) was localized by in situ hybridization on band p113 of chromosome 18. This probe was then used in cytogenetic diagnosis to identify precisely a small supernumerary chromosome as an isochromosome i(18p).

Small supernumerary chromosomes in amniotic cell cultures (two cases)

Small supernumerary chromosomes in amniotic cell cultures (two cases)

Prader-Willi syndrome and chromosome 15. A clinical discussion of 20 cases.

A chromosome 15 anomaly was observed in 12 of 20 patients, 17 of whom were clinically suspected of having Prader-Willi syndrome (PWS). The clinical features of eight cases with 15q11-12 deletion were very similar to those originally described in PWS. On the other hand, the group of normal karyotype patients is heterogeneous, and their features do not strictly correspond to the clinical definition of PWS. However, the hypothesis that PWS is associated with deletion of 15q11-12 can neither explain the apparently balanced translocations of chromosome 15 nor account for the small supernumerary metacentric chromosomes corresponding to an isochromosome 15 for band 15q11 observed in some cases.

Characteristic behaviour of the ring chromosome

A case of a 5½-yr-old girl with a tiny supernumerary chromosome fragment found in mosaic is reported. N.M. was referred to the genetics unit for assessment of the clinical significance of the presence of a small supernumerary chromosome fragment. Studies in the department suggested the fragment was a small ring chromosome as demonstrated by the presence of some metaphases with a double-size fragment or 2 single size fragments, and interphase cells showing micronuclei. The characteristic signs observed in cell preparations due to the behaviour of a ring chromosome and the clinical consequences of such a chromosome are discussed.

Differences in laboratory performance between strains ofGlossina morsitans morsitansWestwood from Rhodesia and Tanzania and associated chromosome diversity

AbstractA laboratory colony ofGlossina morsitans morsitansWestw. which originated from puparia collected near Kariba, Rhodesia was more productive than another colony which originated from Handeni, northern Tanzania; during 1975, the former produced an average of 5–9 puparia per female and the latter 3–6. Although mortality in the Tanzanian colony was somewhat higher than in the Rhodesian colony, the main reason for the lower productivity of the Tanzanian colony was the much poorer fecundity of the females. This was associated with abnormalities of the reproductive system. The differences in laboratory performance between the two stocks were probably a reflection of their genetic diversity. Thus the Tanzanian Y chromosome is metacentric compared with the almost acrocentric Y chromosome of Rhodesian males, and some individuals carry small metacentric supernumerary chromosomes which are not present in Rhodesian flies. Giemsa C-banding showed band differences between the chromosome complements of the two stocks. Probably the most important difference, revealed by polytene chromosome analysis, is a large inversion in the X chromosome of Tanzanian flies, which, together with at least one band difference, is fixed in the homozygous condition. The possible evolutionary pathways of these mutations are outlined and their significance is discussed in terms of their distribution in nature and of the performance of the two strains in the laboratory.

Chromosome survey of new patients admitted to the four maximum security hospitals in the United Kingdom.

In a survey of male patients admitted to the four maximum security hospitals in the United Kingdom during 1972 and 1973, 26 out of 611 (4.26%) karyotyped were found to have chromosome abnormalities. Of these, 13 (2.13%) had a 47,XYY abnormality; 5 (0.8%) were chromatin positive but two of these had cell lines that included an extra Y chromosome, one being a 48XXYY male and the other a mosaic 48,XXYY/XYY. Eight patients with autosomal abnormalities included two with Down's syndrome and a 47,XY,+21 karyotype, two with small supernumerary chromosomes, 47,XY+mar, and two with inherited balanced translocation. As in the prevalence studies of patients in these high secruity hospitals, the significant finding was the very high frequency of males with extra Y chromosomes. In this survey, it was most marked in the younger patients and particularly in those who were aged 20 years or less (approximately 6%). As a group the XYY males were therefore significantly younger than all other male admissions. As in previous surveys thay were also significantly taller and 60% were 185 cm or more in height. There were no other distinguishing physical characteristics associated with the 47,XYY karytype. In all but two patients the behaviour disturbances were attributable to psychopathic disorders and mental subnormality was diagnosed no more frequently than in the total population studied (approximately 50%).

BIOSYSTEMATICS OF THE GENUS IPS (COLEOPTERA: SCOLYTIDAE) IN NORTH AMERICA. HOPPING'S GROUPS IV AND X

AbstractThe taxonomic concepts of the Ips species of groups IV and X were tested by controlled breeding, bioassay of sex pheromone specificity, and examination of morphological and karyological details. No changes were made in the status of Ips pini, I. bonanseai, and I. avulsus of group IV. I. interstitialis of group X is removed from synonymy with I. calligraphus, and I. ponderosae, also previously considered a synonym of I. calligraphus, is assigned subspecific rank. Assertions of close phylogenetic relationship of the Eurasian I. duplicatus and I. sexdentatus with groups IV and X, respectively, are rejected.I. pini from widely separated localities were interfertile although egg hatchability was subnormal in some crosses involving F1 from matings of beetles from western and eastern North America. I. pini and I. bonanseai readily mated but less than 3% of the eggs hatched and the larvae died. There was no evidence of breeding incompatibility in crosses of I. c. calligraphus from Florida and California or I. c. ponderosae from New Mexico and South Dakota. However, hatchability differed drastically between reciprocal pairings of the I. calligraphus subspecies, possibly as a result of cytoplasmic incompatibility. All eggs produced in pairings of I. interstitialis with either of the I. calligraphus subspecies failed to hatch.First meiotic metaphase of I. pini, I. bonanseai, and both I. calligraphus subspecies invariably showed the formula 15AA + Xyp. This karyotypic formula also applied to I. avulsus except for a few individuals that had 2 small supernumerary chromosomes. The karyotype of I. interstitialis was not determined. Heteromorphic bivalents and univalents were detected in hybrids of the I. calligraphus subspecies.Cross attractiveness to sex pheromones was demonstrated for I. pini from different regions, for I. pini and I. bonanseai, and for the I. calligraphus subspecies. When samples of attractive frass from eastern and western I. pini males were presented simultaneously, eastern females responded equally to both samples but western females favored western frass by a margin of 2 to 1. Similarly, I. c. calligraphus clearly discriminated in favor of consubspecific pheromone while I. c. ponderosae did not.The locality of several of Eichhoff’s holotypes is noted.

SEX AND SUPERNUMERARY CHROMOSOMES IN THE DIOECIOUS GRASSSOHNSIA FILIFOLIA

A dioecious grass Sohnsia filifolia (Fourn.) Airy Shaw (Syn. Calamochloa filifolia Fourn.) from Mexico has been found to have 2n = 20 chromosomes in both male and female plants. The staminate plants have one chromosome much longer than the other chromosomes of the complement. One pistillate plant was found to have 30 chromosomes, among which the largest chromosome is quite similar to the largest component of the diploid male plant. The longest chromosome has been designated as the Y chromosome. An XY-mechanism of the Drosophilia type has been suggested for the sex determination system in this species. One small supernumerary chromosome was observed in the microsporocytes of some male plants, but was absent in roots.