cisgénesis/intragénesis - inicio · • la biotecnología y en particular las plantas gm tienen...
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CISGéNESIS/INTRAGéNESIS
CICLO: NUEVAS TECNICAS DE MEJORAMIENTO GENETICO
Dr. Jorge M. Santamaría F.
CIBIOGEM, 29 Agosto 2014
Unidad de Biotecnología, CICY 1
Introducción • Las producción de alimentos implica un enorme reto en una
población mundial creciente. El problema se acentúa en escenarios de cambio climático que puede impactar en forma importante la capacidad de producción de alimentos.
• La Biotecnología y en particular las plantas GM tienen un potencial importante en el mejoramiento genético de cultivos, particularmente en lo que se refiere a ograr variedades resistentes a enfermedades y tolerantes a factores abióticos, que merman su productividad
• Sin embargo, una de las mayores preocupaciones sobre los cultivos transgénicos, es el uso de genes foráneos.
• Como alternativa, se sugirió apenas hace 10 años, las técnicas de intragénesis (Rommens et al., 2004) y hace apenas 8 años, la cisgénesis (Schouten et al., 2006), en donde solo se utilizarían genes de la misma planta o de especies sexualmente compatibles con la que se fuera a mejorar.
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Preguntas a contestar durante el seminario:
• ¿Que son los INTRA y CIS génicos?
• ¿Que diferencias tienen en relación a los transgénicos?
• ¿Como se desarrollaron?
• ¿Que avances se tienen hasta ahora?
• ¿Deben ser des-regulados?
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1) ¿Qué SON? DEFINICIONES IMPORTANTES
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Cisgenicas, Schouten, 2006 Intragénicas, Rommens 2004
• Traditional breeding
• Encompasses all plant breeding methods that do not fall under current GMO regulations.As the European legal framework defines GMOs and specifies various breeding techniques that are excluded from the GMO regulations,we use this framework as a starting point, particularly the European Directive 2001/18/EC on the deliberate release of GMOs into the environment (European Parliament, 2001).
• Excluded from this GMO Directive are longstanding cross breeding, in vitro fertilization, polyploidy induction, mutagenesis and fusion of protoplasts from sexually compatible plants
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Schouten et al., EMBO Reports VOL 7 | NO 8 | 2006
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Transgenesis
•Is the genetic modification of a recipient plant with one
or more genes from any non-plant organism, or from a
donor plant that is sexually incompatible with the recipient
plant.
•This includes gene sequences of any origin in the anti-
sense orientation, any artificial combination of a coding
sequence and a regulatory sequence, such as a promoter
from another gene, or a synthetic gene.
Schouten et al., EMBO Reports VOL 7 | NO 8 | 2006
• Cisgenesis
• Is the genetic modification of a recipient plant with a natural gene from a crossable —sexually compatible—plant.
• Such a gene includes its introns and is flanked by its native promoter and terminator in the normalsense orientation.
• Cisgenic plants can harbour one or more cisgenes, but they do not contain any transgenes. 7
Schouten et al., EMBO Reports VOL 7 | NO 8 | 2006
CIS-GEN
• The cisgene
• Is an identical copy of a gene from the sexually compatible pool including promoter, introns and terminator. When using Agrobacterium mediated transformation , the cisgene is inserted within Agrobacterium derived T-DNA borders (Schouten et al., 2006).
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Definiciones de acuerdo a Schouten, Krens & Jacobsen, Embo Rep. 2006
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Definiciones de acuerdo a EFSA Report 2012
• Cisgenesis
• Cisgenesis is the genetic modification of a recipient organism with a gene from a crossable - sexually compatible – organism (same species or closely related species).
• This gene includes its introns and is flanked by its native promoter and terminator in the normal sense orientation.
• Cisgenic plant
• Plant created using technique of cisgenesis.
• Cisgene
• Gene introduced into a recipient organism by genetic modification and originating from a crossable - sexually compatible – organism (same species or closely related species). This gene includes its introns and is flanked by its native promoter and terminator in the normal sense. 10
Autoridad Europea Seguridad Alimentos EFSA, 2012
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Definiciones… • Intragenesis
• Allows in vitro recombination of elements isolated from different genes within the sexually compatible gene pool
• Furthermore, there is no requirement for introns and cDNA or fragments of genes can be used.
• Thus both expression and silencing intragenic constructs can be designed.
• Rommens et al., 2004; Holme et al., 2013)
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CM Rommens et al., Plant Phys. 2004
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2) ¿En que difieren los INTRA y CIS génicos, de los TRANSgénicos?
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¿Qué similitudes y diferencias tienen los INTRA y los CIS génicos entre ellos ?
Holme et al., Plant Biotech J, 2013
Figure 1. Illustration of cisgene and intragene constructs as defined by Schouten and coworkers in 2006 and Rommens in 2004 , respectively.
• The cisgene is an identical copy of a gene from the sexually compatible pool including promoter, introns and terminator (a, b). When using Agrobacterium mediated transformation, the cisgene is inserted within Agrobacterium derived T-DNA borders.
• Intragenesis allows in vitro recombination of elements isolated from different genes within the sexually compatible gene pool (a, c). Furthermore, there is no requirement for introns and cDNA or fragments of genes can be used. Thus both expression and silencing intragenic constructs can be designed. According to the definition of Rommens, the intragene should be inserted within borders isolated from the sexually compatible DNA pool (P-DNA borders), when using Agrobacterium mediated transformation.
• The figure is copied from the Plant Biotechnology Journal
Desde el punto de vista del origen de los genes, la cisgénesis es similar al mejoramiento convencional
SIMILITUDES Y DIFERENCIAS entre CIS e INTRA génesis (basado en Holme et al., 2013)
SIMILITUDES DIFERENCIAS
Ambos difieren de transgénicos ya que no contienen genes foráneos
La intragénesis permite recombinación in vitro de varios elementos genéticos funcionales
•Ambos contienen genes que provienen de especies sexualmente compatibles
Los CIS contienen los intrones del gen a introducir, los INTRA no requieren intrones
Ambos no deben tener promotores ni terminadores foráneos
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Holme et al., Plant Biotech J, 2013
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Holme et al., 2013
One of the major concerns of the general public about transgenic crops relates to the mixing of genetic materials between species that cannot hybridize by natural means. To meet this concern, the two transformation concepts cisgenesis and intragenesis were developed as alternatives to transgenesis.
Both concepts imply that plants must only be transformed with genetic material derived from the species itself or from closely related species capable of sexual hybridization. Furthermore, foreign sequences such as selection genes and vector-backbone sequences should be absent.
Intragenesis differs from cisgenesis by allowing use of new gene combinations created by in vitro rearrangements of functional genetic elements.
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Holme et al., 2013
Several surveys show higher public acceptance of intragenic/cisgenic crops compared to transgenic crops. Thus, although the intragenic and cisgenic concepts were introduced internationally only 9 and 7 years ago, several different traits in a variety of crops have currently been modified according to these concepts. Five of these crops are now in field trials and two have pending applications for deregulation.
Currently, intragenic/cisgenic plants are regulated as transgenic plants worldwide. However, as the gene pool exploited by intragenesis and cisgenesis are identical to the gene pool available for conventional breeding, less comprehensive regulatory measures are expected. The regulation of intragenic/cisgenic crops is presently under evaluation in the EU and in the US regulators are considering if a subgroup of these crops should be exempted from regulation. It is accordingly possible that the intragenic/cisgenic route will be of major significance for future plant breeding.
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3) ¿Cual es el estatus actual de intra y cis génicos…?
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INTRAGENICOS 2004 Caius M Rommens
J. R. Simplot Company, Boise, Idaho 83706, USA.
Rommens CM, Humara JM, Ye J, et al. 2004. Crop improvement through modification of the plant’s own genome. Plant Physiology 135: 421– 431. Rommens CM, Haring MA, Swords K, Davies HV, Belknap WR. 2007. The intragenic approach as a new extension to traditional plant breeding. Trends in Plant Science 12: 397–403.
CM Rommens et al., 2007
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CM Rommens et al., 2007
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CM Rommens, JAFC, 2007
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CM Rommens, JAFC, 2007 • New crop varieties are developed by applying traditional breeding methods
that rely on random genome modifications. These varieties combine multiple traits that support farm efficiency and acceptable yields but also contain genes associated with the production of toxins, allergens, and/or antinutritional compounds that were not considered during the selection process.
• Furthermore, existing cultivars frequently lack the functional genes required for specific sensory traits and the formation of health-promoting antioxidants. One new method efficiently addresses some of these issues by either silencing undesirable genes or enhancing the expression of genes that are linked to dormant beneficial traits.
• Rather than incorporating foreign DNA into the plant’s genome, these methods transform crops with plant-derived transfer (P-) DNAs that consist of only native genetic elements. The genetic modification can be characterized molecularly so that any inadvertent transfer of undesirable DNA, as may be the case with traditional methods, is excluded.
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Rommens, JAFC, 2007
• A recently developed intragenic potato plant is silenced for the polyphenol oxidase, dikinase R1, and phosphorylase-L genes in a tuberspecific manner. French fries derived from these tubers lack discolorations, display an enhanced potato flavor, and produce greatly reduced amounts of the suspected carcinogen acrylamide.
• It is argued that intragenic modification is unlikely to trigger phenotypic, biochemical, or physiological variation that is new to the species. Similarly, the targeted traits are similar to those that breeders select for and often have a history of domestication and reduced fitness.
• For these reasons, an updated regulatory system is proposed whereby intragenic crops are considered as low risk and should be cleared for commercial release in a timely and cost-effective manner.
• By using modern techniques to modify the same genetic material that is used by breeders, intragenic approaches may be perceived as an acceptable extension of traditional methods in crop improvement.
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HJ (Henk) Schouten Wageningen NL, 2006
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Schouten et al., 2006
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El desarrollo de una manzana cisgénica Vanblaere et al., 2011
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El desarrollo de una manzana cisgénica Vanblaere et al., 2011
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1. Cisgenesis represents a step toward a new generation of GM crops. The lack of selectable genes (e.g. antibiotic or herbicide resistance) in the final product and the fact that the inserted gene(s) derive from organisms sexually compatible with the target crop should rise less environmental concerns and increase consumer’s acceptance.
2. Here we report the generation of a cisgenic apple plant by inserting the endogenous apple scab resistance gene HcrVf2 under the control of its own regulatory sequences into the scab susceptible apple cultivar Gala.
3. A previously developed method based on Agrobacterium-mediated transformation combined with a positive and negative selection system and a chemically inducible recombination machinery allowed the generation of apple cv. Gala carrying the scab resistance gene HcrVf2 under its native regulatory sequences and no foreign genes.
4. Three cisgenic lines were chosen for detailed investigation and were shown to carry a single T-DNA insertion and express the target gene HcrVf2.
5. This is the first report of the generation of a true cisgenic plant.
El desarrollo de una manzana cisgénica, Vanblaere et al., 2011
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Schouten et al., TreeGenGenom 2014
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Caracterización fenotípica, Bioquímica y Molecular de la manzana cisgénica resistente a Scab (Jänsch et al., PMBR 2014)
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Caracterización Molecular de manzana cisgénica desarrollada (Vanblaere et al., PBJ, 2014)
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Summary
Using resistance genes from a crossable donor to obtain cultivars resistant to diseases and the use of such cultivars in production appears an economically and environmentally advantageous approach. In apple, introgression of resistance genes by classical breeding results in new cultivars, while introducing cisgenes by biotechnological methods maintains the original cultivar characteristics. Recently, plants of the popular apple ‘Gala’ were genetically modified by inserting the apple scab resistance gene Rvi6 (formerly HcrVf2) under control of its own regulatory sequences.
This gene is derived from the scab-resistant apple ‘Florina’ (originally from the wild apple accession Malus floribunda 821). The vector used for genetic modification allowed a postselection marker gene elimination to achieve cisgenesis. In this work, three cisgenic lines were analysed to assess copy number, integration site, expression level and resistance to apple scab.
For two of these lines, a single insertion was observed and, despite a very low expression of 0.07- and 0.002-fold compared with the natural expression of ‘Florina’, this was sufficient to induce plant reaction and reduce fungal growth by 80% compared with the scab-susceptible ‘Gala’. Similar results for resistance and expression analysis were obtained also for the third line, although it was impossible to determine the copy number and TDNA integration site–such molecular characterization is requested by the (EC) Regulation No. 1829/2003, but may become unnecessary if cisgenic crops become exempt from GMO regulation.
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Desarrollo de una papa cisgénica resistente al tizón tardío
Jo et al, BMC Biotechnology 2014
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• Abstract
• Background: Phytophthora infestans, causing late blight in potato, remains one of the most devastating pathogens in potato production and late blight resistance is a top priority in potato breeding. The introduction of multiple resistance (R) genes with different spectra from crossable species into potato varieties is required. Cisgenesis is a promising approach that introduces native genes from the crops own gene pool using GM technology, thereby retaining favourable haracteristics of established varieties.
• Results: We pursued a cisgenesis approach to introduce two broad spectrum potato late blight R genes, Rpi-sto1 and Rpi-vnt1.1 from the crossable species Solanum stoloniferum and Solanum venturii, respectively, into three different potato varieties. First, single R gene-containing transgenic plants were produced for all varieties to be used as references for the resistance levels and spectra to be expected in the respective genetic backgrounds. Next, a construct containing both cisgenic late blight R genes (Rpi-vnt1.1 and Rpi-sto1), but lacking the bacterial kanamycin resistance selection marker (NPTII) was transformed to the three selected potato varieties using Agrobacterium-mediated transformation. Gene transfer events were selected by PCR among regenerated shoots. Through further analyses involving morphological evaluations in the greenhouse, responsiveness to Avr genes and late blight resistance in detached leaf assays, the selection was narrowed down to eight independent events. These cisgenic events were selected because they showed broad spectrum late blight resistance due to the activity of both introduced R genes. The marker-free transformation was compared to kanamycin resistance assisted transformation in terms of T-DNA and vector backbone integration frequency. Also differences in regeneration time and genotype dependency were evaluated.
• Conclusions: We developed a marker-free transformation pipeline to select potato plants functionally expressing a stack of late blight R genes. Marker-free transformation is less genotype dependent and less prone to vector backbone integration as compared to marker-assisted transformation. Thereby, this study provides an important tool for the successful deployment of R genes in agriculture and contributes to the production of potentially durable late blight resistant potatoes.
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Holme et al, ISB NR, 2013
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Papa, Manzana, Fresa, Uva… (Holme et al, ISB NR, 2013)
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Álamo, Centeno, Alfalfa, Trigo y Cebada (Holme et al, ISB NR, 2013)
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14 casos; mayor resistencia enfermedades, mayor tolerancia a sequia o mejoramiento calidad
(Holme et al, ISB NR, 2013)
• CISGENICOS
Papa, Manzana, Alamo2, Trigo, Cebada,
• INTRAGENICOS
Papa1, Fresa, Uva3, Centeno3, Alfalfa
Aunque algunos de ellos solo Parcialmente: • 1Aun conservan el terminador NOS de A. tumefaciens • 2Aun conservan genes marcadores • 3Aun conservan genes marcadores, promotores y terminadores, de especies no relacionadas
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Cisgenicos o intragénicos Liberados pruebas en campo (Holme et al, 2009)
EUROPA
Currently in field trials in EU
• Potatoes
– with high amylopectin
– with resistance to late blight,
• Apple
– with increased resistance to scab,
• Barley
– with improved phytase activity
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Cisgenicos o intragénicos Liberados pruebas en campo (Holme et al, 2009)
En Estados Unidos: currently undergoing field trials In USA,
• Potatoes with improved processing qualities
• Furthermore, JR Simplot recently petitioned the U.S. Department of Agriculture
(USDA) to deregulate a potato with:
all the previously described intragenic modifications, i.e.,
– reduced black spot bruise, slow degradation of starch to sugar during storage, and low asparagine to reduce the acrylamide level in processed potatoes.
• Thus, although intra-/cisgenic crops are still regulated under the same regulatory guidelines as transgenic crops worldwide,
• One of the intragenic developments may presently be close to commercial application.
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Argumentos en contra…
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Dennis Eriksson1, Sten Stymne2 & Jan K Schjoerring1, Carta al editor Nature Biotechnology, 2014 1Department of Plant and Environmental Sciences, Copenhagen University, Frederiksberg, Denmark. 2Department of Plant Breeding, Swedish University of Agricultural Sciences,
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Eriksson et al., 2014 Cisgenesis is a creative attempt to get some GM crops into commercialization
‘through the backdoor’, several research groups are lately promoting the concept of cisgenesis as an alternative to transgenesis2.
We would counter that there are no scientific indications of either risk or unpredictability associated with the phylogenetic distance between the DNA donor and recipient.
The only raison d’être for this conceptual diversification is thus a somewhat arbitrary notion of unnaturalness in the mixing of unrelated genetic material in a fashion that cannot occur without human assistance.
We would further point out that the idea of naturalness in plant breeding became obsolete already at the turn of the 19th century when scientific progress and particularly Mendelian genetics, rather than farm-based bulk selections, were adopted as the main drivers of crop improvement.
The exploration of heterosis enabled an agronomically superior mix of alleles, and the introduction of induced mutations as an approach later created a vast wealth of novel genetic variation.
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Eriksson et al., 2014 • The promotion of cisgenesis as a replacement for transgenesis is nothing less than a giant
leap backwards in the historical progress of plant breeding.
• even if cisgenics would deliver this proposed benefit, the strategy also poses risks and additional costs:
• First, the adoption of a cisgenic strategy over a transgenic one will involve the need to invest yet more resources (purely for the purpose of circumventing discriminatory regulations). The expertise and time needed to create case-specific genomic clones that include endogenous promoters and terminators, free from selectable marker genes and vector backbones, should not be underestimated.
• Second, rather than promoting public understanding of scientific principles, adoption of the approach may be seen as tacit agreement with the nonscientific view that there is something inherently unnatural and risky with the cross-kingdom transfer of genetic material. This strictly philosophical notion is not based on current scientific knowledge. As a consequence, it reinforces prejudice and discrimination against transgenic crops.
• Therefore, if the postulated cisgenesis concept alone is exempted from the regulation that currently applies to GM crop plants, we would enter a slippery slope that inexorably leads away from objective and unbiased scientific principles. 54
Eriksson et al., 2014
• Finally,
• There is a danger that the promotion of cisgenesis would result in a backlash in the trust that the public places in its scientific institutions.
• If cisgenic plants are really less risky than transgenic plants, people may start to ask, why have scientific institutions consistently made a stand for several decades that transgenic crops are no more inherently risky than conventionally bred crops? 55
Argumentos a favor…
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Jacobsen & Schouten, 2008
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Jacobsen & Schouten, 2008
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Jacobsen & Schouten, 2008
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Jacobsen & Schouten, 2008
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Morris & Spillane, 2008
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Kuzma & Kotovich, 2011 Embo reports
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Kuzma & Kotovich, 2011
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Kuzma & Kotovich, 2011
Podevin et al., 2012 EMBO REPORT
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• Definitions according to the EU working group on new techniques:
• Cisgenesis is genetic modification of a recipient organism with a gene (cisgene) from a crossable—sexually compatible—organism;
• Intragenesis is genetic modification of a recipient organism
that involves the insertion of a reorganized, full or partial coding region of a gene combined frequently with a promoter and/or terminator from another gene of the same species or a crossable species;
• ZFN3 technique targets delivery of transgenes (insertions) by homologous recombination;
• Grafting a non-genetically modified scion onto a genetically modified rootstock results in a fruit that does not contain the insert. 67
Podevin et al., 2012
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Podevin et al., 2012
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• Importantly, the regulatory environment needs to support innovation, wider policy objectives and consumer acceptance of NPPs.
• Therefore, regulatory systems for NPPs need to be dynamically scalable to the rate of innovation and advances in the field, remain proportionate to the level of risk that the use of the technology might pose, prevent harm without jeopardizing other policy objectives, support international harmonization and avoid disparities in risk assessment practices.
• This in itself is a major challenge, and there is no time to further delay discussion among experts in the scientific community with the public and stakeholders.
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Podevin et al., 2012 Conclusiones
Telem et al, 2013 Current Genomics
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Telem et al, 2013 • Abstract:
• The implication of molecular biology in crop improvement is now more than three decades old. Not surprisingly, technology has moved on, and there are a number of new techniques that may or may not come under the genetically modified (GM) banner and, therefore, GM regulations.
• In cisgenic technology, cisgenes from crossable plants are used and it is a single procedure of gene introduction whereby the problem of linkage drag of other genes is overcome.
• The gene used in cisgenic approach is similar compared with classical breeding and cisgenic plant should be treated equally as classically bred plant and differently from transgenic plants.
• Therefore, it offers a sturdy reference to treat cisgenic plants similarly as classically bred plants, by exemption of cisgenesis from the current GMO legislations.
• This review covers the implications of cisgenesis towards the sustainable development in the genetic improvement of crops and considers the prospects for the technology.
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• CONCLUSION (Telem et al, 2013)
• Application of cisgenic techniques enhances the possibility to introgress the preferred genes into the novel cultivars (mostly single gene in the first step), without disturbing their favorable characteristics.
• Therefore, the most compelling contribution of cisgenesis may be anticipated for the development of monogenic resistance traits. But, the application of gene pyramiding will also accomplish a more durable resistance. Major advantages could be expected in breeding of plants with long life spans such as trees. Traits such as abiotic stress tolerance are usually complex (e.g. due to polygenic traits). The introgression of one gene or QTL is usually not sufficient to engineer stress-tolerant lines [62]. Gene pyramiding will be necessary in this aspect, implying that the sequences and functions of genes are well characterized.
• The information regarding cisgenesis is very rare and there is only certain frivolous information given in the seminars and conference proceedings.
• Thus, if we expand our area of research towards cisgenic approach and if it has been exempted from the regulatory framework of GM technology it is anticipated that cisgenesis may wipe out the likely uncertain outcomes and the social beliefs that public have in their mind regarding GM technology.
• Therefore, cisgenesis will be playing an important role in sustainable crop improvement. 73
Holme et al, ISB NR, 2013
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En Europa (EFSA)… (Holme et al, 2013 ISB)
• Presently, there actually seems to be willingness in the EU to at least make assessments on whether deregulating these technologies could be feasible in the future.
• Recently, the European Commission (EC) requested EFSA (European Food Safety Authority) to evaluate possible hazards posed by crops generated through cisgenesis and intragenesis as compared to crops generated by conventional breeding and transgenesis.
• In the resulting report, EFSA concluded that modifications made by all four techniques can produce unintended hazardous effects, attributable to the source of the gene, the trait, and general changes in structure of the plant genome.
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En Europa (EFSA)… Holme et al, 2013 ISB
• Importantly, in comparison to conventional breeding they concluded that cisgenesis will lead to similar hazards while
• Both intragenesis and transgenesis may lead to novel hazards not associated with conventional breeding.
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En Estados Unidos (EPA) Holme et al, 2013 ISB
• Similarly in the US, there seems to be a willingness to discuss these techniques and a subgroup of cisgenic crops engineered to express plant protectants was recently
proposed to be exempted from regulation by the US Environmental Protection Agency.
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En Estados Unidos … (Holme et al, 2013 ISB)
• Furthermore, JR Simplot recently petitioned the U.S.
Department of Agriculture (USDA) to deregulate a potato
with:
All the previously described intragenic modifications, i.e.,
– reduced black spot bruise, slow degradation of starch to sugar during storage, and low asparagine to reduce the acrylamide level in processed potatoes.
• Thus, although intra-/cisgenic crops are still regulated under the same regulatory guidelines as transgenic crops worldwide, one of
the intragenic developments may presently be close to commercial application.
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Conclusión (Holme et al, 2013 ISB)
• However, although a less rigid regulation may not be achieved in the near future, the development of intra-/cisgenic crops may yet address the concerns of the public, and may therefore facilitate a new dialogue among scientists, breeding companies, and the public regarding genetically engineered plants.
• Increased confidence in these novel crops may facilitate a qualified discussion of the potential environmental, economic, and health benefits of genetically engineered plants, and of their possible contribution to address the global need for more efficient and sustainable crop production.
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Si recuerdan, al principio del seminario nos hicimos varias preguntas:
1. ¿Que son los INTRA y CIS génicos?
2. ¿Que diferencias tienen en relación a los transgénicos?
3. ¿Como se desarrollaron?
4. ¿Que avances se tienen hasta ahora?
5. ¿Deben ser desregulados?
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Algunas respuestas…
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1) ¿Que son? • CISGENICAS Se introducen genes de la misma planta o de plantas que
sean sexualmente compatibles. Se introduce el gen completo con promotor y terminador nativo.
Se argumenta que deben considerarse similares a las
variedades obtenidas por mejoramiento convencional y debe considerarse el desregularlos.
La Cisgénesis parece una técnica muy prometedora para
trasformar plantas con nuevos caracteres relevantes y así, desarrollar plantas genéticamente modificadas, pero mas amigables para el consumidor y el ambiente.
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1) ¿Que son? • INTRAGENICAS
También se introducen genes de especies que sean sexualmente compatibles.
Del pool de genes de especies que sean sexualmente compatibles, se puede utilizar el promotor de uno de los genes, el terminador de otro, y la secuencia codificante de interés de un tercer gen, etc.
La Intragénesis ofrece mayor flexibilidad y tal vez mayor eficiencia en el logro de un genotipo con las características deseables, que los cisgénicos.
Sin embargo, pudieran tener menor aceptación pública que los cisgénicos.
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2) ¿Que diferencias tienen en relación a los transgénicos?
Que no usan genes foráneos (ni promotores, ni terminadores), que no sean de especies sexualmente compatibles.
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3) ¿Como se desarrollaron?
• Como una alternativa a la percepción pública sobre la incertidumbre que ha generado el uso de genes de especies no relacionadas, en la generación de plantas genéticamente modificadas.
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4) ¿Que avances se tienen hasta ahora?
Se trata de técnicas relativamente recientes (10 años). Sin embargo se ha avanzado en las capacidades técnicas.
En algunos cultivos actualmente ya se están haciendo pruebas de campo:
Papa y Manzana: cisgénicas en Europa
Papa: intragénica en USA.
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5) ¿Deben ser desregulados?
Varios grupos de investigación internacionales proponen que los cisgénicos deben ser considerados como modificaciones equivalentes a los logrados con el mejoramiento genético convencional y por lo tanto, deben tener un trato diferente en materia de regulación.
Es importante mencionar que un estudio de la EASF concluye que los
cisgénicos no representan nuevos riesgos que los del mejoramiento tradicional, pero que los intragénicos fueron considerados por ellos, como que si pueden presentar nuevos riesgos, no asociados al mejoramiento convencional.
De cualquier forma, tanto en Europa como en USA, ya se están efectuando
pruebas en campo tanto con CIS como con INTRA génicos de papa y manzana.
De hecho, en USA ya existe una solicitud de desregulación de una papa obtenida por intragenésis.
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Comentario final
• La producción de alimentos en México representa grandes retos. Es importante lograr la autosuficiencia alimentaria de cultivos básicos, debiendo incrementar la resistencia a enfermedades y la tolerancia a sequia y altas temperaturas en cultivos estratégicos.
• El uso de cisgénicos e intragénicos puede ser una alternativa para afrontar algunos de esos retos.
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Comentario final… • Por lo que por un lado, se debe favorecer la
investigación en Centros de Investigación Nacionales, que conlleve al desarrollo de capacidades técnicas para ofrecer nuevas variedades resistentes a enfermedades, tolerantes a sequía y calor, y con mejor contenido nutracéutico, usando estas y otras técnicas de la Biotecnología actual.
• Y por otro lado, como se está haciendo en EUROPA y en USA, en México se debe discutir (invetigadores y reguladores) y evaluar si los cisgénicos y los intragénicos, puedan considerarse como una forma de mejoramiento genético con menor riesgo, y evaluar si deben tener un tratamiento diferente en materia de regulación. 90
GRACIAS
• Dr. Jorge M. Santamaría F
• Unidad de Biotecnología
• CICY
• www.cicy.mx
• Tel (999) 9428330 Ext. 203
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