Genetic aspects of animal reasoning

This paper reviews the investigations of Prof. L. V. Krushinsky and his colleagues into the genetics of complex behaviors in mammals. The ability of animals to extrapolate the direction of a food stimulus movement was investigated in wild and domesticated foxes (including different fur-color mutants), wild brown rats, and laboratory rats and mice. Wild animals (raised in the laboratory) were shown to be superior to their respective domesticated forms on performance of the extrapolation task, especially in their scores for the first presentation, in which no previous experience could be used. Laboratory rats and mice demonstrated a low level of extrapolation performance. This means that only a few laboratory animals were capable of solving the task, i.e., the percentage of correct solutions was equivalent to chance. The brain weight selection program resulted in two mice strains with a 20% (90-mg) difference in brain weight. Ability to solve the extrapolation task was present in low-brain weight mice in generations 7–11 but declined with further selection. Investigation of extrapolation ability in mice with different chromosomal anomalies demonstrated that animals with Robertsonian translocations Rb(8,17) 1lem and Rb(8,17) 6Sic were capable of solving this task in a statistically significant majority of cases, while mice with fusion of other chromosomes, as well as CBA normal karyotype mice, performed no better than expected by chance. Mice with two types of partial trisomies and animals homo- and heterozygous for translocations were also tested. Although mice with T6 trisomy performed no better than expected by chance, animals with trisomy for a chromosome 17 fragment solved the task successfully. Thus, a genetic component underlying the ability to solve the extrapolation task was demonstrated in three animal species. The extrapolation task in animals is considered to reveal a general capacity for elementary reasoning. The genetic basis of this capacity is very complex.     

Pallister-Hall syndrome associated with an unbalanced chromosome translocation

We report 3 cases of Pallister-Hall syndrome involving hypothalamic hamartoblastoma, hypopituitarism, cranial, and limb abnormalities. The first 2 cases represent the first apparent sibs reported with this syndrome. Patient 1 represents the first known patient with this syndrome with an abnormal karyotype.     

Molecular characterization of a complex translocation in a newborn infant

A newborn infant was referred because of low-set ears, mild downward slant of the palpebral fissues, micrognathia with higharched palate, a flat midface, small mouth, and thin upper lip with cupid bow configuration. To some extent her cry resembled that associated with cri du chat syndrome. Cytogenetic findings with G- and Q-banding alone failed to characterize precisely the complex translocations. By the chromosome in situ suppression (CISS) hybridization technique using whole chromosome specific probes, a complex 4 breakpoint rearrangement involving both arms of a single chromosome 1 with the long arms of chromosome 5 and 11 was disclosed, i.e., 46,XX, der(1),t(1;5) t(1;11) (5qter→5q31::1p31.3→1q44::11q23→11qter;5pter→5q31::1p31.3→1pter;11pter→11q23::1q44→1qter). Gene deregulation and position effect may explain the multiple anomalies in individuals with apparently balanced translocations may shed some light towards unveiling the clinical consequences associated with aberrations which are presumably balanced. © 1993 Wiley-Liss, Inc.     

OGD增加小鼠离体海马组织内cPKCβII和nPKCε的膜转位

目的:通过观察无糖低氧(OGD)刺激对小鼠海马脑片内蛋白激酶C(PKC)特定亚型膜转位水平(激活程度)的影响,进一步证实我们在整体低氧预适应小鼠模型上所获实验结果,并为离体海马脑片缺血/低氧预适应(I/HPC)模型建立及后续药物干预实验打下基础。方法:急性分离小鼠海马组织、制备400!μm厚度的脑片,并用无糖低氧(OGD)人工脑脊液(ACSF)模拟缺血/低氧刺激;应用SDS-PAGE和Westernbolt等生化技术,并结合GelDoc凝胶成像系统,半定量检测OGD刺激2、5、10、15和30min后海马脑片内cPKCβII和nPKCε的膜转位水平。结果:OGD刺激可增高海马脑片内cPKCβII和nPKCε的膜转位水平,且这种增高从刺激5min开始持续至30min均有显著差异(P<0.001,n=6)。结论:实验结果进一步证实cPKCβII和nPKCε可能参与脑缺血/低氧性预适应的形成过程,并提示OGD10min作为制备离体海马脑片I/HPC模型的预处理刺激较为合理。     

Ultrastructural studies of spermatozoa from infertile males with Robertsonian translocations and 18, X, Y aneuploidies

BACKGROUND: In order to clarify the relationship between chromosomal rearrangements, sperm morphology and interchromosomal effects (ICE), we studied the spermatogenetic defects in seven infertile Robertsonian translocation carriers. METHODS: Lymphocyte karyotypes were evaluated using Giemsa-Trypsin-Giemsa banding and fluorescence in-situ hybridization (FISH). Semen analysis was performed by light and transmission electron microscopy. FISH of sperm nuclei was carried out to detect possible ICE. RESULTS: Lymphocyte karyotype analysis revealed five t(13;14), one t(13;21) and one t(14;22) carriers. Sperm ultrastructural examination highlighted a higher percentage of immaturity, apoptosis and necrosis than in controls. Aneuploidies of gonosomes were detected in sperm from five out of six carriers of Robertsonian translocation, whereas aneuploidy of chromosome 18 was evident in three out of six carriers. The frequencies of diploidy were altered in all cases. CONCLUSIONS: Since these infertile patients showed severe spermatogenetic impairment from the morphological and meiotic points of view, we recommend detailed sperm ultrastructural and chromosomal analysis before undertaking ICSI cycles in Robertsonian translocation carriers.     

Cytogenetics of a new cytotype of African Mus (subgenus Nannomys) minutoides (Rodentia, Muridae) from Kenya: C- and G- banding and distribution of (TTAGGG) n telomeric sequences

We present the results of a cytogenetic study on Mus (Nannomys) minutoides from Kenya by means of C- and G- banding and in-situ fluorescence hybridization (FISH) to localize the telomeric sequences. The karyotype is characterized by the occurrence of several Rb chromosomes Rb(1.X), Rb(1.Y). Rb(2.17), Rb(3.13), Rb(4.10), Rb(5.11), Rb(6.7), Rb(8.12), not previously described for this species. This finding suggests a high level of chromosomal diversification, which means it is possible to consider this cytotype as a new, well-differentiated, chromosomal lineage within the subgenus. The C-banding of the metaphases illustrated conspicuous blocks of centromeric heterochromatin at the paracentromeric regions of all telocentric chromosomes. Centromeric heterochromatin is not visible on all biarmed chromosomes. Following hybridization with telomeric probes, bright interstitial telomeric sequence (ITS) fluorescence signals are evident at the pericentromeric area of all Rb chromosomes, with the exception of Rb(2.17). Considering the localization of the C-positive heterochromatin and of the telomeric sequences, the events leading to the Kenyan cytotype from an all-telocentric condition probably included two steps: first, fusion without loss of heterochromatin and pericentromeric telomeric sequences; second, the reduction of the C-positive satellite DNA followed by the amplification of telomeric sequences in the C-negative paracentromeric region of Rb chromosomes. The presence of a single Rb(2.17) without ITS indicates possible variations of this mechanism.     

PMX2B,a new candidate gene for Hirschsprung's disease

Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNF and NTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3 and ECE-1), the SOX10 gene and the SIP1 gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50-60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with a de novo t(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.     

Partial trisomy 3q syndrome inherited from familial t(3;9)(q26.1; p23)

A five-year-old girl was referred to prometaphase chromosome analysis because of mental retardation, facial dysmorphic features suggestive of Cornelia de Lange syndrome, cleft palate and additional minor congenital malformations of the cardiac system and fingers and toes. A familial balanced translocation (3;9)(q26.1; p23) was found. The karyotype of the proposita was 46,XX,der(9),t(3;9)(q26.1;p23). Thus the patient was trisomic for 3q26.1-qter and monosomic for 9p23-pter. The unbalanced chromosome constitution was not detected by standard Q-banding analysis shortly after birth. The karyotype was misdiagnosed as 46,XX,9(p+) in the proposita and her mother, and thought to be a normal variant of chromosome 9. The repeated cytogenetic study led to the diagnosis of the translocation and to the possibility of prenatal diagnosis in the translocation carriers. A survey of 22 published cases of dup(3q) showed that nearly 60% were secondary to familial balanced rearrangements with an excess of maternally derived abnormal chromosomes 3. Red blood cell galactose-1-phosphate-uridyltransferase (GALT) activity was normal in the patient, consistent with previous assignment of the gene locus for GALT to 9p13 (Shih et al. 1982).     

Meiotic behaviour of a new complex X-Y-autosome translocation and amplified heterochromatin in Jumnos ruckeri (Saunders) (Coleoptera, Scarabaeidae, Cetoniinae)

Species belonging to the Cetoniinae subfamily studied so far possess 20 chromosomes, including a small X and a punctiform Y: 20,Xyp in the males. In a series of species from the Goliathini tribe under study we found a very unusual karyotype, with 12 autosomes and large sex chromosomes (14,neoXY) in Jumnos ruckieri from Thailand. Applying various techniques including pachytene bivalent spreading, we showed that 40% (mitotic and meiotic prophases) to 60% (metaphases) of the karyotype length was composed of heterochromatin. Both sex chromosomes were NOR carriers. At pachynema they underwent a complete synapsis of their distal regions, indicating their autosomal origin. At contrast, their very uneven central regions remained separated, but associated with nucleolus material. This association persisted until diakinesis, forming a pseudo-chiasma between the neoX and the neoY, which were always in end-to-end association. Compared to free autosomes the autosomal parts of the neo-sex chromosomes had a significant lack of interstitial chiasmata, indicating a possible lack of recombination at their proximal regions. As in the cases of X-autosome translocations in mammals, autosomal and gonosomal parts of the neo-sex chromosomes were insulated by heterochromatin, which may be a necessary condition to avoid deleterious position effects, whatever the mechanisms of gene dosage compensation.     

10, 15 reciprocal translocation in an infertile man: ultrastructural and fluorescence in-situ hybridization sperm study: case report

BACKGROUND: Peculiar sperm defects are described in a sterile man heterozygous for a balanced translocation t(10;15) (q26;q12). As this structural reorganization was absent in the parents, the translocation must have appeared de novo in the present patient. METHODS: Spermatozoa were analysed under light and transmission electron microscopy (TEM). Fluorescence in-situ hybridization (FISH) was performed on the lymphocyte karyotype. Aneuploidy frequencies of chromosomes 18, X and Y in sperm nuclei, not involved in the translocation, were investigated using three-colour FISH. Dual- colour FISH was used to evaluate segregation of chromosomes 10, 15 in decondensed sperm nuclei. Moreover, three-colour FISH, using telomeric probes for chromosomes 10, 15 was performed in order to distinguish balanced and unbalanced gametes. RESULTS AND CONCLUSIONS: Overall, structural characteristics indicate general immaturity of the germinal cells. FISH sperm analysis detected an increase in chromosome 18 disomy (0.81%) suggesting an interchromosomal effect. A high frequency of diploidies, particularly 18,18,X,X and 18,18,X,Y, was also found. FISH segregation analysis for chromosomes 10, 15 indicated that 32.8% were balanced gametes, whereas 68.2% were unbalanced. Taken together, these data demonstrate in a male carrier of a reciprocal translocation t(10;15) the presence of diffuse ultrastructural sperm alterations and a high frequency of sperm aneuploidies. The existence of a correlation among these factors is proposed.