Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely distributed in nature, th... more Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely distributed in nature, that cleave sialic acid residues from the oligosaccharide components of glycoconjugates. All of the sialidase enzymes thus far characterized share an Asp block, repeated three to five times in the primary structure, and an F/YRIP sequence motif that is part of the active site. Using a sequence homology-based approach, we have identified a novel human gene, named NEU2, mapping to chromosome 2q37. The nucleotide sequence analysis of the gene has shown that it contains only one intron of about 1.25 kb, and the longest open reading frame encodes a protein of 380 amino acids, with a two-Asp block consensus, and the YRIP sequence. In the putative promoter sequence there are a classical TATAA box and four E boxes, which are consensus binding sites for muscle-specific transcription factors. Northern blot analysis revealed expression of the NEU2 transcript only in skeletal muscle.
By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci... more By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA.
Summary: Purpose: The chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phe... more Summary: Purpose: The chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phenotypical markers. We describe the electroclinical pattern in a group of patients with r(20).Methods: We observed 3 patients (a boy, patient 1; his mother, patient 2; and an unrelated man, patient 3), performing prolonged video-EEG and cytogenetic studies and fluorescent in situ hybridization (FISH) with chromosome-specific telomeric probes.Results: All 3 patients had a very similar abnormal electroclinical pattern characterized by long bursts or trains of rhythmic theta waves, which were sharply contoured or had a notched appearance (with no detectable clinical correlate), and generalized spike waves (SW) associated with seizures of probable frontotemporal origin (SFT). In all 3 patients, the cytogenetic analysis of T lymphocytes showed mosaicism with a normal cell line and a second cell line with a chromosome 20, although the latter was little represented in patients 2 and 3. A few cells with a single chromosome 20 were also found. The same cytogenetic findings were confirmed in the lymphoblastoid cell line of patient 1 and in the fibroblasts of patient 3. FISH with chromosome-specific telomeric probes and TTAGGG sequences demonstrated the integrity of the ring chromosomes.Conclusions: The clinical picture of these patients appears to be related to the instability of the r(20)-generating cells monosomic for chromosome 20 and is thus haploinsufficient for a gene. In these patients, the electroclinical pattern of theta waves (probably unrelated to epilepsy) and the SW and SFT, even with mild mental retardation (MR) or no MR and without dysmorphic features, suggest that the r(20) syndrome may be present.
Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemi... more Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.
BACKGROUND: Chromosomal rearrangements in Xq are frequently associated with premature ovarian fai... more BACKGROUND: Chromosomal rearrangements in Xq are frequently associated with premature ovarian failure (POF) and have defined a POF 'critical region'. Search for genes responsible for the disorder has been elusive. METHODS: We report mapping of novel breakpoints of X;autosome-balanced translocations and interstitial deletions and a review of published X chromosome rearrangements. RESULTS: All the novel POF-associated rearrangements were mapped outside and often very distant from genes. The majority mapped to a gene-poor region in Xq21. In the same region, deletions were reported in women who apparently did not have problems conceiving. Expression analysis of genes flanking breakpoints clustered in a 2-Mb region of Xq21 failed to demonstrate ovary-specific genes. CONCLUSIONS: Our results excluded most of the possible explanations for the POF phenotype and suggested that POF should be ascribed to a position effect of the breakpoints on flanking genes. We also showed that while the X breakpoint may affect X-linked genes in the distal part of Xq, from Xq23 to Xq28, interruption of the critical region in Xq21 could be explained by a position effect of the Xq critical region on genes flanking the autosomal breakpoints.
We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carryi... more We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carrying a heterozygous subtle mutation in the LIS1 gene. Six patients showed a mutation predicted to encode for a truncated protein, and one mutation altered a splicing site, resulting in skipping of exon 4. Western blot analysis performed on the lymphoblastoid cell line of 2 patients bearing truncating mutations indicated that the mutated allele did not produce a detectable amount of the LIS1 protein; whereas the analysis performed on the fibroblasts from the patient with a splice-site mutation was suggestive of partial protein synthesis from the mutated allele. Although clinical and magnetic resonance imaging findings of patients with truncating mutations did not differ from those observed in patients with a heterozygous deletion, the patient bearing the exon-skipping mutation had less severe clinical and brain involvement. Our data suggest that truncating mutations in the LIS1 gene are relatively common among patients with classical lissencephaly not bearing a heterozygous deletion at 17p13.3, and strengthen the relevance of correct intracellular dosage of the LIS1 protein in the neuronal migration process.
Background-Cytogenetic evidence suggests that the haploinsufficiency of Ն1 gene located in 8p23 b... more Background-Cytogenetic evidence suggests that the haploinsufficiency of Ն1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. Methods and Results-We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at Ϸ10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at Ϸ10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. Conclusions-Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs. (Circulation. 2000;102:432-437.)
The distribution of (TTAGGG)n telomeric repeats was studied in chromosomes of two Atlantic eels,A... more The distribution of (TTAGGG)n telomeric repeats was studied in chromosomes of two Atlantic eels,Anguilla anguilla andA. rostrata. We found that these sequences hybridize to all the telomeres but also to the entire nucleolar organizer region (NOR) localized in both species at the short arm of chromosome 8. This was considered to be due to the interspersion of telomeric sequences within the NOR ones. Whatever the significance of this interspersion may be, it seems to be limited toA. anguilla andA. rostrata since inMuraena helena (family muraenidae), which also belongs to the Anguilliformes, no telomeric hybridization signals were found along the NOR regions.
to that region Kelley et By screening an expressed sequence tag database, Augusseau et al., 1986;... more to that region Kelley et By screening an expressed sequence tag database, Augusseau et al., 1986; we identified a novel human gene, SLC7A4, encoding . a solute carrier family 7 [cationic amino acid (CAA) designed a deletion map of the 22q11 region, genotyp-CAT-4 transporter, y / system] member 4. The SLC7A4 ing 61 VCFS patients. This work allowed the identifi-cDNA is 2325 nt long and includes 78, 1911, and 336 nt cation of the minimal critical region of VCFS, a 400-kb in the 5 noncoding, coding, and 3-noncoding regions, DNA segment spanning between the D22S941 and the respectively. SLC7A4 displays high homology with D22S944 microsatellites. Several genes were isolated SLC7A1 and SLC7A2, two previously known CAA from both the minimal and the commonly deleted retransporters. By chromosomal in situ hybridization gion, which is a larger DNA segment (2-3 Mb) deleted and YAC identification, SLC7A4 was mapped to in a considerable number of patients. A few clinical 22q11.2, the commonly deleted region of the velocardistudies failed to clearly correlate both the extension ofacial syndrome (VCFS, Shprintzen syndrome). In a and the location of the deleted region with the phenopatient affected by VCFS, deletion of SLC7A4 was demtype Bonnet et al., 1997). onstrated by chromosomal FISH. By Northern analy-Transport of the cationic amino acids (CAA), i.e., arsis, an abundant transcript was detected in brain, tesginine, lysine, and ornithine, in mammalian cells octis, and placenta. Microinjection of SLC7A4 mRNA into curs by a system designated ''system y / '' (White et al., Xenopus laevis oocytes demonstrates a significant stimulation of CAA transport. ᭧ 1998 Academic Press 1982)
We report four cases of subjects with phenotypic abnormalities and mental retardation associated ... more We report four cases of subjects with phenotypic abnormalities and mental retardation associated with apparently balanced translocations, two inherited and two de novo, which showed, by molecular analysis, a hidden complexity. All the cases have been analyzed with different molecular techniques, including array-CGH, and in two of them the translocation breakpoints have been defined at the level of base pairs via studies in somatic hybrids containing single derivative chromosomes. We demonstrated that all the translocations were in fact complex rearrangements and that an imbalance was present in three of them, thus accounting for the phenotypic abnormalities. In one case, a Prader–Willi subject, we were not able to determine the molecular cause of his phenotype. This study, while confirming previous data showing unexpected complexity in translocations, further underscores the need for molecular investigations before taking for granted an apparently simple cytogenetic interpretation.
We studied the case of a subject with an inverted duplication of 40 cM of 2q33-q37 concurrent wit... more We studied the case of a subject with an inverted duplication of 40 cM of 2q33-q37 concurrent with a 10 cM deletion of the distal 2q, the latter not being detectable by cytogenetics. Microsatellite analysis demonstrated the absence of maternal alleles in the deleted region and a double dosage for one of the maternal alleles in the duplication region. We hypothesised that this type of rearrangement occurs at meiosis I, while the two homologues are synapsed for most of their length. The presence of inverted duplicons in the same chromosome arm would favour the partial refolding of one homologue into itself so leading to the intrachromatid synapsis and recombination of the inverted repeats. The arising recombinant chromosome is deleted for the region beyond the most distal repeat and with the chromatids joined together at the level of the region located between the two duplicons. At meiosis II, the two linked chromatids can join the opposite poles provided that a breakage between the two centromeres occurs leading to a duplicated/deleted chromosome and a simply deleted chromosome. This model can be extended to all the so-called inverted duplication cases and to part of the terminal deletions. In fact the finding that, in our invdup(2q), the entire 40 cM duplication region involves only one of the two maternal alleles, indeed indicates that the abnormal crossover occurs between sister chromatids. The phenotype associated with our 2q rearrangement led us to narrow the critical region for the Albright-like syndrome to 10 cM in the subterminal 2q region.
Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely distributed in nature, th... more Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely distributed in nature, that cleave sialic acid residues from the oligosaccharide components of glycoconjugates. All of the sialidase enzymes thus far characterized share an Asp block, repeated three to five times in the primary structure, and an F/YRIP sequence motif that is part of the active site. Using a sequence homology-based approach, we have identified a novel human gene, named NEU2, mapping to chromosome 2q37. The nucleotide sequence analysis of the gene has shown that it contains only one intron of about 1.25 kb, and the longest open reading frame encodes a protein of 380 amino acids, with a two-Asp block consensus, and the YRIP sequence. In the putative promoter sequence there are a classical TATAA box and four E boxes, which are consensus binding sites for muscle-specific transcription factors. Northern blot analysis revealed expression of the NEU2 transcript only in skeletal muscle.
By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci... more By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA.
Summary: Purpose: The chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phe... more Summary: Purpose: The chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phenotypical markers. We describe the electroclinical pattern in a group of patients with r(20).Methods: We observed 3 patients (a boy, patient 1; his mother, patient 2; and an unrelated man, patient 3), performing prolonged video-EEG and cytogenetic studies and fluorescent in situ hybridization (FISH) with chromosome-specific telomeric probes.Results: All 3 patients had a very similar abnormal electroclinical pattern characterized by long bursts or trains of rhythmic theta waves, which were sharply contoured or had a notched appearance (with no detectable clinical correlate), and generalized spike waves (SW) associated with seizures of probable frontotemporal origin (SFT). In all 3 patients, the cytogenetic analysis of T lymphocytes showed mosaicism with a normal cell line and a second cell line with a chromosome 20, although the latter was little represented in patients 2 and 3. A few cells with a single chromosome 20 were also found. The same cytogenetic findings were confirmed in the lymphoblastoid cell line of patient 1 and in the fibroblasts of patient 3. FISH with chromosome-specific telomeric probes and TTAGGG sequences demonstrated the integrity of the ring chromosomes.Conclusions: The clinical picture of these patients appears to be related to the instability of the r(20)-generating cells monosomic for chromosome 20 and is thus haploinsufficient for a gene. In these patients, the electroclinical pattern of theta waves (probably unrelated to epilepsy) and the SW and SFT, even with mild mental retardation (MR) or no MR and without dysmorphic features, suggest that the r(20) syndrome may be present.
Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemi... more Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.
BACKGROUND: Chromosomal rearrangements in Xq are frequently associated with premature ovarian fai... more BACKGROUND: Chromosomal rearrangements in Xq are frequently associated with premature ovarian failure (POF) and have defined a POF 'critical region'. Search for genes responsible for the disorder has been elusive. METHODS: We report mapping of novel breakpoints of X;autosome-balanced translocations and interstitial deletions and a review of published X chromosome rearrangements. RESULTS: All the novel POF-associated rearrangements were mapped outside and often very distant from genes. The majority mapped to a gene-poor region in Xq21. In the same region, deletions were reported in women who apparently did not have problems conceiving. Expression analysis of genes flanking breakpoints clustered in a 2-Mb region of Xq21 failed to demonstrate ovary-specific genes. CONCLUSIONS: Our results excluded most of the possible explanations for the POF phenotype and suggested that POF should be ascribed to a position effect of the breakpoints on flanking genes. We also showed that while the X breakpoint may affect X-linked genes in the distal part of Xq, from Xq23 to Xq28, interruption of the critical region in Xq21 could be explained by a position effect of the Xq critical region on genes flanking the autosomal breakpoints.
We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carryi... more We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carrying a heterozygous subtle mutation in the LIS1 gene. Six patients showed a mutation predicted to encode for a truncated protein, and one mutation altered a splicing site, resulting in skipping of exon 4. Western blot analysis performed on the lymphoblastoid cell line of 2 patients bearing truncating mutations indicated that the mutated allele did not produce a detectable amount of the LIS1 protein; whereas the analysis performed on the fibroblasts from the patient with a splice-site mutation was suggestive of partial protein synthesis from the mutated allele. Although clinical and magnetic resonance imaging findings of patients with truncating mutations did not differ from those observed in patients with a heterozygous deletion, the patient bearing the exon-skipping mutation had less severe clinical and brain involvement. Our data suggest that truncating mutations in the LIS1 gene are relatively common among patients with classical lissencephaly not bearing a heterozygous deletion at 17p13.3, and strengthen the relevance of correct intracellular dosage of the LIS1 protein in the neuronal migration process.
Background-Cytogenetic evidence suggests that the haploinsufficiency of Ն1 gene located in 8p23 b... more Background-Cytogenetic evidence suggests that the haploinsufficiency of Ն1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. Methods and Results-We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at Ϸ10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at Ϸ10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. Conclusions-Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs. (Circulation. 2000;102:432-437.)
The distribution of (TTAGGG)n telomeric repeats was studied in chromosomes of two Atlantic eels,A... more The distribution of (TTAGGG)n telomeric repeats was studied in chromosomes of two Atlantic eels,Anguilla anguilla andA. rostrata. We found that these sequences hybridize to all the telomeres but also to the entire nucleolar organizer region (NOR) localized in both species at the short arm of chromosome 8. This was considered to be due to the interspersion of telomeric sequences within the NOR ones. Whatever the significance of this interspersion may be, it seems to be limited toA. anguilla andA. rostrata since inMuraena helena (family muraenidae), which also belongs to the Anguilliformes, no telomeric hybridization signals were found along the NOR regions.
to that region Kelley et By screening an expressed sequence tag database, Augusseau et al., 1986;... more to that region Kelley et By screening an expressed sequence tag database, Augusseau et al., 1986; we identified a novel human gene, SLC7A4, encoding . a solute carrier family 7 [cationic amino acid (CAA) designed a deletion map of the 22q11 region, genotyp-CAT-4 transporter, y / system] member 4. The SLC7A4 ing 61 VCFS patients. This work allowed the identifi-cDNA is 2325 nt long and includes 78, 1911, and 336 nt cation of the minimal critical region of VCFS, a 400-kb in the 5 noncoding, coding, and 3-noncoding regions, DNA segment spanning between the D22S941 and the respectively. SLC7A4 displays high homology with D22S944 microsatellites. Several genes were isolated SLC7A1 and SLC7A2, two previously known CAA from both the minimal and the commonly deleted retransporters. By chromosomal in situ hybridization gion, which is a larger DNA segment (2-3 Mb) deleted and YAC identification, SLC7A4 was mapped to in a considerable number of patients. A few clinical 22q11.2, the commonly deleted region of the velocardistudies failed to clearly correlate both the extension ofacial syndrome (VCFS, Shprintzen syndrome). In a and the location of the deleted region with the phenopatient affected by VCFS, deletion of SLC7A4 was demtype Bonnet et al., 1997). onstrated by chromosomal FISH. By Northern analy-Transport of the cationic amino acids (CAA), i.e., arsis, an abundant transcript was detected in brain, tesginine, lysine, and ornithine, in mammalian cells octis, and placenta. Microinjection of SLC7A4 mRNA into curs by a system designated ''system y / '' (White et al., Xenopus laevis oocytes demonstrates a significant stimulation of CAA transport. ᭧ 1998 Academic Press 1982)
We report four cases of subjects with phenotypic abnormalities and mental retardation associated ... more We report four cases of subjects with phenotypic abnormalities and mental retardation associated with apparently balanced translocations, two inherited and two de novo, which showed, by molecular analysis, a hidden complexity. All the cases have been analyzed with different molecular techniques, including array-CGH, and in two of them the translocation breakpoints have been defined at the level of base pairs via studies in somatic hybrids containing single derivative chromosomes. We demonstrated that all the translocations were in fact complex rearrangements and that an imbalance was present in three of them, thus accounting for the phenotypic abnormalities. In one case, a Prader–Willi subject, we were not able to determine the molecular cause of his phenotype. This study, while confirming previous data showing unexpected complexity in translocations, further underscores the need for molecular investigations before taking for granted an apparently simple cytogenetic interpretation.
We studied the case of a subject with an inverted duplication of 40 cM of 2q33-q37 concurrent wit... more We studied the case of a subject with an inverted duplication of 40 cM of 2q33-q37 concurrent with a 10 cM deletion of the distal 2q, the latter not being detectable by cytogenetics. Microsatellite analysis demonstrated the absence of maternal alleles in the deleted region and a double dosage for one of the maternal alleles in the duplication region. We hypothesised that this type of rearrangement occurs at meiosis I, while the two homologues are synapsed for most of their length. The presence of inverted duplicons in the same chromosome arm would favour the partial refolding of one homologue into itself so leading to the intrachromatid synapsis and recombination of the inverted repeats. The arising recombinant chromosome is deleted for the region beyond the most distal repeat and with the chromatids joined together at the level of the region located between the two duplicons. At meiosis II, the two linked chromatids can join the opposite poles provided that a breakage between the two centromeres occurs leading to a duplicated/deleted chromosome and a simply deleted chromosome. This model can be extended to all the so-called inverted duplication cases and to part of the terminal deletions. In fact the finding that, in our invdup(2q), the entire 40 cM duplication region involves only one of the two maternal alleles, indeed indicates that the abnormal crossover occurs between sister chromatids. The phenotype associated with our 2q rearrangement led us to narrow the critical region for the Albright-like syndrome to 10 cM in the subterminal 2q region.
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Papers by Elena Rossi