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PubMed2000

Somatic versus germline mutation processes at minisatellite CEB1 (D2S90) in humans and transgenic mice.

The most variable human minisatellites show extreme germline instability dominated by complex intra-allelic rearrangements plus a lower frequency of inter-allelic transfers of repeat units. In contrast, little is known about somatic instability at such loci. We have therefore used single-molecule PCR to analyze mutation at minisatellite CEB1 (D2S90) in human blood DNA. Somatic mutants were rare and involved only relatively simple intra-allelic events, with no bias toward expansions, in sharp contrast to the complex gain-biased rearrangements seen in sperm. Somatic and germline mutation processes were further analyzed in mice transgenic for a cosmid insert containing CEB1. Mutant molecules in transgenic sperm and blood were detected but only at the low frequencies seen in human blood and arose mainly by simple duplications and deletions as seen for somatic mutations in human. These data suggest distinct pathways for germline and somatic CEB1 mutations with germline instability involving recombination-based repair of meiotic double-strand breaks and somatic mutation arising by replication slippage or mitotic recombination. The problem of transferring germline-specific features of minisatellite instability from human to mouse suggests, with other recent observations, that long-range chromatin conformation may be required for the recombination-based mode of germline instability at human minisatellites.

Alleles↗
PubMed2002

Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.

The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of the primary tumor and in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII) showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR) displayed alterations in some tumor regions but not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7 and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor suggests that these phenomena may act together in HNPCC tumorigenesis. Furthermore, the observed intratumoral heterogeneity of mutations in coding repeats implies these changes occur late in tumorigenesis and, thus, probably play a role in tumor progression rather than initiation.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Frequent somatic mutations of hMSH3 with reference to microsatellite instability in hereditary nonpolyposis colorectal cancers.

hMSH3 is one of the human DNA mismatch repair genes but has not yet been reported to be associated with hereditary nonpolyposis colorectal cancer. Recently, somatic mutation at a polyadenine tract, i.e., (A)8, in hMSH3 was reported in cancers with microsatellite instability (MI). To clarify the tumorigenetic role of hMSH3, we screened for somatic mutations at the hMSH3 (A)8 repeat in 29 tumors from 23 hereditary nonpolyposis colorectal cancer patients. One or two A deletions in the (A)8 repeat were found in 11 (57.9%) of the 19 MI-positive tumors but not in 10 MI-negative ones, indicating secondary mutations after germline mutations of other mismatch repair genes. Moreover, the MI frequency of three or more nucleotide repeats was higher in hMSH3 (A)8-mutated tumor cells than in nonmutated ones (p<0.05). These data suggest that a mutation of a mismatch repair gene enhances the frequency of another mismatch repair gene mutation, such as of hMSH3, resulting in severe MI.

Adult↗
PubMed2001

Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene.

Huntington's disease (HD) is a neurodegenerative disorder characterized by the expansion of CAG repeats in exon 1 of the HD gene. To clarify the instability of expanded CAG repeats in HD patients, an HD model mouse has been generated by gene replacement with human exon 1 of the HD gene with expansion to 77 CAG repeats. Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues. One or two CAG repeat expansion was found in litters from paternal transmission, whereas contraction of CAG repeat in litters was observed through maternal transmission. Elderly mice show greater CAG repeat instability than younger mice, and a unique case was observed of an expanded 97 CAG repeat mouse. Somatic CAG repeat instability is particularly pronounced in the liver, kidney, stomach, and brain but not in the cerebellum of 100-week-old mice. The same results of expanded CAG repeat instability as observed in this HD model mouse were confirmed in the human brain of HD patients. Glial fibrillary acidic protein (GFAP)-positive cells have been found to be increased in the substantia nigra (SN), globus pallidus (GP), and striatum (St) in the brains of 40-week-old affected mice, although without neuronal cell death. The CAG repeat instability and increase in GFAP-positive cells in this mouse model appear to mirror the abnormalities in HD patients. The HD model mouse may therefore have advantages for investigations of molecular mechanisms underlying instability of CAG repeats.

Age Factors↗
PubMed1991

Intergeneric somatic hybridization in Gramineae: somatic hybrid plants between tall fescue (Festuca arundinacea Schreb.) and Italian ryegrass (Lolium multiflorum Lam.).

Tall fescue (Festuca arundinacea Schreb.) protoplasts, inactivated by iodoacetamide, and non-morphogenic Italian ryegrass (Lolium multiflorum Lam.) protoplasts, both derived from suspension cultures, were electrofused and putative somatic hybrid plants were recovered. Two different genotypic fusion combinations were carried out and several green plants were regenerated in one of them. With respect to plant habitus, leaf and inflorescence morphology, the regenerants had phenotypes intermediate between those of the parents. Southern hybridization analysis using a rice ribosomal DNA probe revealed that the regenerants contained both tall fescue- and Italian ryegrass-specific-DNA fragments. A cloned Italian ryegrass-specific interspersed DNA probe hybridized to total genomic DNA from Italian ryegrass and from the green regenerated somatic hybrid plants but not to tall fescue. Chromosome counts and zymograms of leaf esterases suggested nuclear genome instability of the somatic hybrid plants analyzed. Four mitochondrial probes and one chloroplast DNA probe were used in Southern hybridization experiments to analyze the organellar composition of the somatic hybrids obtained. The somatic hybrid plants analyzed showed tall fescue, additive or novel mtDNA patterns when hybridized with different mitochondrial gene-specific probes, while corresponding analysis using a chloroplast gene-specific probe revealed in all cases the tall fescue hybridization profile. Independently regenerated F. arundinacea (+) L. multiflorum somatic hybrid plants were successfully transferred to soil and grown to maturity, representing the first flowering intergeneric somatic hybrids recovered in Gramineae.

Cells, Cultured↗
PubMed2001

Microsatellite stability in human post-mortem tissues.

Human identification and forensic criminal casework may involve DNA profiling of decomposed material. Somatic microsatellite (STR) instability may lead to false exclusions and theoretically to false inclusions, both in criminal cases and in human identification. Hence, the somatic and postmortal stability of the actual sequences is crucial to the reliability of such analyses. Somatic STR stability in human tissues has been documented in small series only and the effect of postmortal tissue decomposition on microsatellite stability remains to be elucidated. On this basis, we have systematically searched for somatic STR mutations in 26 deceased humans without signs of decomposition at autopsy and 25 autopsy cases with obvious signs of postmortal decomposition. A blood sample and six tissue samples were collected from each case. Seven STRs were chosen for study, the tetranucleotides HUMVWA31/A, HUMTH01, HUMF13A1, and HUMFES/FPS, and the hyperpolymorphic markers HUMAPOAI1, D11S554 and HUMACTBP2. Denaturing gel electrophoresis was performed on an ABD Prism 377 gene sequencer with Genescan 672 software (Applied Biosystems, Inc.). The bone DNA profile of each case was chosen as the standard DNA profile. All cases gave profiles from additional tissues. By intraindividual comparison of DNA profiles in the cases without signs of degradation we find that the short repetitive sequences under study are stable, that is without evidence of somatic mutations. The cases with varying degree of decomposition display postmortal microsatellite stability, we detect no somatic mutations or other possible postmortal changes that could lead to between-organ non-matches. In conclusion, PCR-based STR analyses are suitable in human identification and forensic casework dealing with different tissues, even when the substrate is heavily decomposed.

Autopsy↗
PubMedDate not supplied

[Detection of genomic instability in offspring of male mice chronically exposed to gamma-radiation by the "adaptive response" test].

The genomic instability (GI) in somatic cells of the progeny (F1 generation) of male mice chronically exposed to low-dose gamma-radiation was studied by comparative analysis of chromosome damage. BALB/C male mice exposed to 0.1 Gy (0.01 Gy/day) and 0.5 Gy (0.01 and 0.05 Gy/day) were mated with unirradiated females 15 days after irradiation. For comparison of radiosensitivity, two-month-old males, the descendants of irradiated and unirradiated animals, were subjected to irradiation with a dose of 1.5 Gy (0.47 Gy/min) from a 60Co source. GI was revealed by the standard scheme of adaptive response. The experiments indicated that, by using the test "adaptive response", it is possible to detect the transition of gamma-radiation-induced genomic instability in sex cells of male parent into somatic cells of mice (F1 generation) either from changes in radiosensitivity or by the absence of the adaptive response induced by a standard scheme.

Adaptation, Physiological↗
PubMed1992

Fragile-X syndrome: unique genetics of the heritable unstable element.

The fragile site at Xq27.3 is an unstable microsatellite repeat, p(CCG)n. In fragile-X syndrome pedigrees, this sequence exhibits variable amplification, the length of which correlates with fragile-site expression. There is a direct relationship between increased p(CCG)n copy number and propensity for instability: individuals having large amplifications exhibit somatic variation due to increased instability. The instability of the p(CCG)n repeat, when transmitted through affected pedigrees, explains the unusual segregation patterns of fragile-X phenotype, referred to as the Sherman paradox. All individuals of fragile-X genotype were found (where testing was possible) to have a parent with amplified p(CCG)n repeat, indicating that few, if any, cases of fragile-X syndrome are not familial.

Blotting, Southern↗
PubMed2003

Identification of novel genes with somatic frameshift mutations within coding mononucleotide repeats in colorectal tumors with high microsatellite instability.

We have systematically retrieved genes with coding mononucleotide repeats from sequence databases and analyzed them for mutations in tumors with high levels of microsatellite instability (MSI-H). We found somatic frameshift mutations in 7/13 genes previously not analyzed in MSI-H tumors. According to the frequency of mutations in MSI-H tumors, these genes could be divided into genes with high coding mononucleotide repeat instability (CMRI-H) and genes with low coding mononucleotide instability (CMRI-L). CMR-H genes were mutated in more than 9/38 and CMRI-L in less than 4/38 of MSI-H tumors. Four genes in our study were CMRI-H and could thus possibly play a role in the development of MSI-H tumors: TFE3 (9/38), TEF4 (12/38), RGS12 (11/38), and TCF1 (12/38). Our results suggest that systematic identification of genes with CMR in the sequence databases and determination of mutation frequency in MSI-H tumors might be a powerful tool for identification of new molecular targets in the development of MSI-H tumors.

Adenocarcinoma↗
PubMed2005

Chromosomal instability in the cattle clones derived by somatic cell nuclear-transfer.

Cytogenetic analysis was performed on peripheral lymphocytes collected from 20 cattle clones (19 showed no overt phenotypic abnormalities except for high birth weight while 1 exhibited left forelimb contracture), the donor cell cultures from which they were derived and lymphocytes from six insemination produced control cattle. All animals and cell cultures had a modal chromosome number of 60. The frequency of abnormal cells for donor cell cultures, clones, and controls was 6.68+/-0.30%, 5.30+/-5.49%, and 5.08+/-1.04%, respectively, and did not differ significantly among the groups. There were, however, two clones derived from different donor cell cultures with high incidences of 21.29% and 20.13%, of abnormal cells consisting of pseudodiploid (near-diploid), near-triploid and near-tetraploid, and tetraploid cells. Among these two clones, one had only a few endoreduplicated nuclei although further studies are necessary to precisely define the cytological origin and nature of the abnormal cells. The clones were evaluated at multiple time points for up to 20 months of age and the incidence of abnormal lymphocytes remained stable indicating that the chromosomally abnormal nuclei found in cloned animals was not a transient event. These results show that the majority of phenotypically normal clones have normal chromosomal make up but that instability of chromosome number can occur in clones that are phenotypically normal. Therefore, cytogenetical evaluation of peripheral lymphocytes and other tissues with follow up of the phenotypical consequences of these abnormalities is warranted even in phenotypically normal clones.

Aging↗
PubMed2004

[Instability of plasmid DNA integrated into mammalian somatic cell genome].

The phenomenon of loosing exogenic DNA from the mammalian somatic cell genome is under investigation. It is found that foreign DNA incorporated into cell genome as a result of transfection by electrophoretion may be lost with the frequency from 1/100 up to 1/100 000 per cell division during cultivation. This effect is not dependent of the nature of cell line and vector DNA. It is actual for different cell lines: A23, human fibroblasts AG 11395, murine embryonic line F9, and for different plasmid vectors: p16, p.39, pATR4 and pcDNA3.1-Higr (WRN). Integration of pDNA into genome and the following loosing of this DNA is registered by selection markers G418 and hygromycin B resistance and gancyclovir sensibility. The presence of foreign DNA in the genome was controlled by PCR. It is found that true foreign DNA deletion from the genome takes place rather than gene expression changes. For closely linked plasmid genes deletion of both genes at once as well as loosing any one gene separately is shown. Thus, the phenomenon of selective deletion of exogenic DNA from genome has been demonstrated for different mammalian cells.

Animals↗
PubMed1993

Congenital genetic instability in colorectal carcinomas.

INTRODUCTION: Oncogenic evolution is probably based on a progressive selection of clonal subpopulations from within a single clone. This selection is supposed to be based on enhanced genetic instability in the genome. In the vast majority of patients this increased lability is supposed to be the result of acquired alterations, and once established, it may contribute to the continuing, genetic instability within the neoplastic cells. It has been postulated, that inborn chromosomal instability is not limited to a few rare syndromes. Indeed, one of the common colorectal cancer (CRC) syndromes, familial adenomatous polyposis (FAP), is supposed to be a chromosomal instability syndrome. Also the hereditary nonpolyposis colorectal cancer syndrome (Lynch Syndrome (LS)) has shown genomic instability. Knudson (1971, 1985) has shown, that the same gene can be involved in both the hereditary form of a cancer and in the sporadic form of the same cancer. Due to the existence of such hereditary chromosomal instability syndromes, inherited genetic instability may be of some importance in the evolution of sporadic colorectal cancers. METHODS: In vitro research on dermal fibroblasts is based on the theory, that all studied cells of an individual carry the same genetic material, irrespective of their in vivo expression. Increased in vitro tetraploidy (IVT+) in skin fibroblast cultures is supposed to be a germinally transmitted expression of genomic instability, with special reference to LS. At the same time the chromosomal aberrations, which occur in neoplasms, can be measured by flow cytometric DNA analysis. The DNA content, thus measured, is supposed to be an expression of somatic acquired genetic instability. Finally, since occult mandibular osteomas have been shown to be associated with FAP, we have investigated a substantial part of our patients with this phenotypical marker. AIM OF STUDY: In CRC the adenoma-carcinoma sequence is widely accepted, and the purpose of our investigation was to find a correlation, if any, between: Changes in adenoma flow cytometric DNA content and histological grade and type of adenomas. Changes in dermal fibroblast IVT+ from adenoma patients and histological grade and type of adenomas. Changes in dermal fibroblast IVT+ and flow cytometrical DNA content in adenomas and carcinomas from the same patients. Furthermore, we wanted to investigate if: The occurrence of IVT+ in skin fibroblasts among patients with CRC was different from that of IVT+ among patients without colorectal neoplasies. The occurrence of IVT+ in skin fibroblasts among patients with CRC was associated with the occurrence of occult mandibular osteomas in the same patients. The occurrence of dermal fibroblast IVT+ conveyed any prognostic significance in CRC patients. RESULTS AND CONCLUSIONS: 1) A significant correlation was found between both the occurrence of skin fibroblast IVT+ and adenoma DNA aneuploidy in relation to the degree of dysplasia and histological type of adenomas. This signifies, that inborn and acquired genetic instability is correlated to the adenoma-carcinoma sequence. IVT+ was found to be correlated to the progression of adenomas to carcinomas and not to the development of adenomas. 2) A direct correlation between IVT+ and adenoma DNA aneuploidy could not be demonstrated. However, among those patients with diploid adenomas and IVT+ 57% showed villous adenomas. Among those patients with diploid adenomas and IVT- only 14% had villous adenomas. This further substantiates the correlation of IVT+ to the adenoma-carcinoma sequence. IVT+ was highly associated with DNA aneuploidy in carcinomas, and since IVT+ was found to be significantly associated with CRC's with a DNA index > or = 1.5, it is suggested that IVT+ mainly is correlated to the early steps in tumor progression. 3) IVT+ was found in 34% of sporadic CRC, and tumor DNA aneuploidy was demonstrated in 73%...

Adenoma↗
PubMed2001

A negative regulator of telomere-length protein trf1 is associated with interstitial (TTAGGG)n blocks in immortal Chinese hamster ovary cells.

Telomeres of mammalian chromosomes are composed of long tandem repeats (TTAGGG)n which bind in a sequence-specific manner two proteins-TRF1 and TRF2. In human somatic cells both proteins are mostly associated with telomeres and TRF1 overexpression resulting in telomere shortening. However, chromosomes of some mammalian species, e.g., Chinese hamster, have large interstitial blocks of (TTAGGG)n sequence (IBTs) and the blocks are involved in radiation-induced chromosome instability. In normal somatic cells of these species chromosomes are stable, indicating that the IBTs are protected from unequal homologous recombination. In this study we expressed V5-epitope or green fluorescent protein (GFP)-tagged human TRF1 in different lines of mammalian cells and analyzed distribution of the fusion proteins in interphase nucleus. As expected, transient transfection of human (A549) or African green monkey cells with GFP-N-TRF1 or TRF1-C-V5 plasmids resulted in the appearance in interphase nuclei of multiple faint nuclear dots containing GFP or V5 epitope which we believe to represent telomeres. Transfection of immortalized Chinese hamster ovary (CHO) cell line K1 which have extremely short telomeres with GFP-N-TRF1 plasmid leads to the appearance in interphase nuclei of large GFP bodies corresponding in number to the number of IBTs in these cells. Simultaneous visualization of GFP and IBTs in interphase nuclei of transfected CHO-K1 cells showed colocalization of both signals indicating that expressed TRF1 actually associates with IBTs. These results suggest that TRF1 may serve as general sensor of (TTAGGG)n repeats controlling not only telomeres but also interstitial (TTAGGG)n sequences.

Animals↗
PubMed2003

Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the ataxin-7 gene. In humans, SCA7 is characterized by marked anticipation due to intergenerational repeat instability with a bias toward expansion, and is thus regarded as the most unstable of the polyglutamine diseases. To study the molecular basis of CAG/CTG repeat instability and its pathological significance, we generated lines of transgenic mice carrying either a SCA7 cDNA construct or a 13.5 kb SCA7 genomic fragment with 92 CAG repeats. While the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. We then went on to generate additional lines of genomic fragment transgenic mice, and observed that deletion of the 3' genomic region significantly stabilized intergenerational transmission of the SCA7 CAG92 repeat. These results suggest that cis-information present on the genomic fragment is driving the instability process. As the SCA7 genomic fragment contains a large number of replication-associated motifs, the presence of such sequence elements may make the SCA7 CAG repeat region more susceptible to instability. Small-pool and standard PCR analysis of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that have been shown to undergo neurodegeneration. As large somatic repeat expansions are absent from the brains of SCA7 cDNA mice, our results indicate that neurodegeneration can occur without marked somatic mosaicism, at least in these mice.

3' Untranslated Regions↗
PubMed1999

Immunogenicity of P/Q-type calcium channel in small cell lung cancer: investigation of alpha1 subunit polyglutamine expansion.

The ectopic expression of neuronal P/Q-type voltage-gated calcium channels in small cell lung carcinoma (SCLC) is thought to induce antisynaptic autoimmunity in the paraneoplastic Lambert-Eaton myasthenic syndrome. The gene CACNL1A4, encoding the principal (alpha1A) subunit of this calcium channel, is mutated in several inherited neurological disorders. One of these disorders (spinocerebellar ataxia, type 6, or SCA-6) involves the expansion of a trinucleotide (CAG) repeat unit. We hypothesized that a somatic CAG repeat instability of this gene in neoplastic cells might generate a non-self epitope capable of initiating autoimmunity to P/Q-type calcium channels. We therefore analyzed the CACNL1A4 gene in SCLC lines established from metastases derived from seven individual patients (four associated with Lambert-Eaton myasthenic syndrome, one associated with myasthenia gravis, and two not associated with neurological autoimmunity). We compared their CAG repeat numbers (determined by polymerase chain reaction (PCR) amplification followed by separation of products on a 6% polyacrylamide/8M urea gel) to published norms and to DNA from a patient with SCA-6. The number of CAG repeats in SCLC DNA fell within a normal range whether or not the neoplasm was complicated by neurological autoimmunity. Therefore, it is unlikely that somatically unstable CAG repeat units in the gene encoding the P/Q-type voltage-gated calcium channel account for this tumor protein's immunogenicity in the Lambert-Eaton myasthenic syndrome.

Autoimmunity↗
PubMed1990

Deficiens, a homeotic gene involved in the control of flower morphogenesis in Antirrhinum majus: the protein shows homology to transcription factors.

Deficiens (defA+) is a homeotic gene involved in the genetic control of Antirrhinum majus flower development. Mutation of this gene (defA-1) causes homeotic transformation of petals into sepals and of stamina into carpels in flowers displaying the 'globifera' phenotype, as shown by cross sections and scanning electronmicroscopy of developing flowers. A cDNA derived from the wild type defA+ gene has been cloned by differential screening of a subtracted 'flower specific' cDNA library. The identity of this cDNA with the defA+ gene product has been confirmed by utilizing the somatic and germinal instability of defA-1 mutants. According to Northern blot analyses the defA+ gene is expressed in flowers but not in leaves, and its expression is nearly constant during all stages of flower development. The 1.1 kb long mRNA has a 681 bp long open reading frame that can code for a putative protein of 227 amino acids (mol. wt 26.2 kd). At its N-terminus the DEF A protein reveals homology to a conserved domain of the regulatory proteins SRF (activating c-fos) in mammals and GRM/PRTF (regulating mating type) in yeast. We discuss the structure and the possible function of the DEF A protein in the control of floral organogenesis.

Amino Acid Sequence↗
PubMed1992

GLOBOSA: a homeotic gene which interacts with DEFICIENS in the control of Antirrhinum floral organogenesis.

GLOBOSA (GLO) is a homeotic gene whose mutants show sepaloid petals and carpelloid stamens. The similarity of Glo mutants to those of the DEFICIENS (DEFA) gene suggests that the two genes have comparable functions in floral morphogenesis. The GLO cDNA has been cloned by virtue of its homology to the MADS-box, a conserved DNA-binding domain also contained in the DEFA gene. We have determined the structure of the wild type GLO gene as well as of several glo mutant alleles which contain transposable element insertions responsible for somatic and germinal instability of Glo mutants. Analyses of the temporal and spatial expression patterns of the DEFA and GLO genes during development of wild type flowers and in flowers of various stable and unstable defA and glo alleles indicate independent induction of DEFA and GLO transcription. In contrast, organ-specific up-regulation of the two genes in petals and stamens depends on expression of both DEFA and GLO. In vitro DNA-binding studies were used to demonstrate that the DEFA and GLO proteins specifically bind, as a heterodimer, to motifs in the promoters of both genes. A model is presented which proposes both combinatorial and cross-regulatory interactions between the DEFA and GLO genes during petal and stamen organogenesis in the second and third whorls of the flower. The function of the two genes controlling determinate growth of the floral meristem is also discussed.

Alleles↗