Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-06-01
2004-04-06
Whisenant, Ethan (Department: 1634)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S024300, C435S006120
Reexamination Certificate
active
06716972
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field
This invention relates to determining the genotype of chickens.
2. Description of the Background Art
The poultry breeding business is of major economic importance in the United States and in most parts of the world. Epidemics of viral infectious disease, for example Marek's disease, in flocks raised for meat or eggs can have a devastating effect to this industry, even in modern facilities. Consequently, development of methods to produce breeding stocks of chickens, whether raised for meat or eggs, which are resistant to disease, is commercially very important.
In chickens, as opposed to most mammals, the particular Mhc haplotypes have readily demonstrated differential influences in the immune response to certain diseases, such as the tumors caused by the highly infectious herpes virus responsible for Marek's disease. Chickens with different Mhc genotypes respond differently to the infectious pathogen of Marek's disease, with potentially deadly consequences to animals possessing a relatively unresponsive Mhc genotype (i.e., two non-protective haplotypes). Determining the Mhc genotype of chickens has therefore become important to the poultry industry, so that disease-resistant strains of chickens can be bred.
In domesticated fowl, the known Mhc genes are organized into two separate linkage groups, B and Rfp-Y.
FIG. 1
provides a schematic map showing the known chicken Mhc genes. The B system comprises polymorphic classical Mhc class I heavy chain, class II beta chain, B-G genes and other genes. The B system has been known as a highly polymorphic blood group system since the early 1940's. Rfp-Y was discovered more recently by DNA hybridizations (Briles et al.,
Immunogenetics
37:408-414 (1993)) and consists of at least two class I heavy chain genes, three class II beta chain genes, a c-type lectin gene and two additional genes of unknown nature. Miller et al.,
Proc. Natl. Acad. Sci. USA
, 91:4397-4401 (1994); Miller et al.,
Proc. Natl. Acad. Sci. USA
93:3958-3962 (1996).
As with the B region, the Rfp-Y gene region is small. At least one Rfp-Y haplotype contains only a single functionally active class I locus. This suggests that disease associations with particular Rfp-Y haplotypes have a similar basis in a small number of loci. In addition, interactions may occur between alleles of the B and Rfp-Y loci. Particular combinations of haplotypes in the two systems therefore may provide optimal disease resistance for a particular disease.
It has already been observed that when the B system provides intermediate disease resistance to Marek's disease, the influence of Rfp-Y genotype can be significant. Wakenell et al.,
Immunogenetics
44:242-245 (1996). This influence may be a direct one wherein the Rfp-Y genes compensate in antigen presentation, however additional interactions could occur between loci in B and Rfp-Y. For example, studies of Mhc Class I loci in mice have shown that antigen presenting molecules have a critical role in controlling the activity of natural killer (NK) cells. Signal peptides cleaved from nascent classical class I polypeptides are presented by at least one non-classical class I molecule and recognized by receptors on NK cells, resulting in modulation of NK cell activity. Natural killer cells are critical in eliminating infected cells in which class I molecule expression has been down-regulated by the infecting pathogen. Having the capacity to detect B and Rfp-Y haplotypes in commercially bred poultry provides a means by which immune responses can be optimized.
In the chicken, the role of particular Mhc haplotypes in disease resistance has been extensively investigated. The influence of the genotype of the Mhc B system and resistance to certain diseases in chickens, for example, Marek's disease, has been documented by several authors. See Hanson et al.,
Poult. Sci
. 46:1268 (1967); Briles et al.,
Science
195:193-195 (1977); Briles et al.,
Science
219:977-979 (1983); Longenecker et al.,
Immunogenetics
3:401-407 (1976); Dietert et al.,
Crit. Rev. Poult. Biol
. 3:111-129 (1991); Kaufman et al.,
Immunol. Rev
. 167:101-117 (1999). Genotyping of the B complex of chickens, however, has focused mostly on particular lines of White Leghorn birds, a breed raised primarily for egg production. Alloantisera used to determine B haplotypes in particular lines of egg-producing chickens do not work well for B haplotyping in other lines of chickens. This is especially true for those lines used in the production of chickens raised for meat which are genetically somewhat distant from layer lines.
Though the immune response in chickens to Marek's disease and other viral pathogens is strongly influenced by B complex genotype, other alleles at other loci, including the Rfp-Y gene cluster, perhaps the NK region and other more poorly characterized regions as well, influence Marek's disease resistance. See Brown et al., Avian Dis. 28:884-899 (1984); Vallejo et al.,
Anim. Genet
. 28:331-337 (1997); Bumstead,
Avian Pathol
. 27:s78-s81 (1998); Kaufman et al.,
Avian Pathol
. 28:s82-s87 (1998); Bumstead,
Rev. Sci. Tech
. 17:249-255 (1998); Yonash et al.,
Anim. Genet
. 30:126-135 (1999). Rfp-Y haplotypes differentially influence disease resistance and immunity in chickens. For example, Pharr et al. showed, in chickens of Cornell line N, that with birds homozygous for B system haplotype, skin graft rejection was greater and occurred more quickly when donor and recipient were mismatched for Rfp-Y than when they were Rfp-Y compatible. Pharr et al.,
Immunogenetics
45:52-158 (1996). Additionally, there is varied evidence for the ability for Rfp-Y differences to stimulate lymphocyte proliferation in vitro (Pharr et al.,
Immunogenetics
45:52-58 (1996); Juul-Madsen et al.,
Immunogenetics
45:345 (1997)), indicating that alloresponses to Rfp-Y may be induced.
The products of Rfp-Y genes have a structure similar but not identical to classical class I molecules. The sequence variability inherent in the Rfp-Y class I molecules themselves is sufficient to inherently elicit this type of allogeneic response, but alternatively these molecules could present some form of polymorphic antigens that serve as a minor histocompatibility antigen and produce the described histocompatibility effect. The Rfp-Y loci may be important in providing molecules that supplement the apparently less than comprehensive antigen presentation provided by the B system loci. Mhc-like genes located outside classical Mhc gene regions are implicated in a number of immune response functions in mammalian species, including selection of T-cell population during development. Adachi et al.,
Proc. Natl. Acad. Sci
. (
USA
) 92:1200-1204 (1995).
The previous work of Wakenell et al. indicates that Rfp-Y haplotypes influence resistance to the commercially important Marek's disease in the chicken. Studies of Rfp-Y influence on Marek's disease virus challenge have produced results indicating that Rfp-Y haplotype affects susceptibility to infection in different B complex backgrounds. Wakenell et al.,
Immunogenetics
44:242-245 (1996). In this study, data comparing incidence of Marek's disease tumors in chickens carrying three different Y system genes showed that the Rfp-Y system exerts an effect on Marek's disease resistance and that the influence of Rfp-Y haplotypes in some combinations may be quantitatively similar to that of the B-F region. See Wakenell et al., page 244. Some conflicting data that has been reported might be due to the particular B and Y complex interactions either accentuating or masking the Rfp-Y effects. See Vallejo et al.,
Anim. Genet
. 28:331-337 (1997).
Genes within B and Rfp-Y both have a demonstrated influence in resistance and susceptibility to a number of diseases, including virally-induced tumors, bacterial infections and infections with protozoan parasites. See, for example, Briles et al.,
Science
195:193-195 (1977); Briles et al.,
Immunogenetics
20:217-226 (1984); Longenecker et al.
Goto Ronald M.
Miller Marcia M.
City of Hope
Rothwell Figg Ernst & Manbeck
Whisenant Ethan
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