In the past five years advances in molecular genetics and the
human genome project have contributed to considerable progress
in the area of pig gene mapping. At present the combined number
of genes and markers on the pig genetic linkage maps is approximately
1800, of which about 250 are genes (Archibald et al. 1994
and personal communication; Marklund et al. 1996a; Rohrer
et al. 1996). In addition, the physical genetic map is
over 500 genes and markers (Yerle, personal communication).
The coverage on these maps is now sufficient to allow researchers
to conduct quantitative trait loci (QTL) linkage analyses. QTL
linkage analyses involve using a genomic scan. Often F2 or backcross
families are used and genotypes are obtained for many (>75)
markers evenly spaced across the genome. Several such experiments
are underway and beginning to produce interesting and useful results.
Candidate gene and comparative mapping approaches have also been
successful in identifying major genes affecting several traits.
Candidate gene analysis is when we choose a gene based on the
physiology of the trait. The candidate gene is assumed to affect
trait performance. Comparative gene analysis allows us to find
"positional candidate genes" in the regions associated
with possible QTL. To date, several major genes have been found
with the candidate gene approach. The purpose of this invited
paper is to review the status of QTL and candidate gene analyses
in the pig and to forecast future developments.
Results will be presented for both QTL and candidate gene analyses
in terms of growth and performance, meat quality, disease resistance
and reproduction traits. Many of the results are relatively new
and further analyses are needed to confirm them.
Growth and performance
The first successful large QTL analysis was conducted using a
Wild Boar and Large White three generation family and revealed
major QTL accounting for 20% of the phenotypic variance for average
backfat and abdominal fat on chromosome 4 (Andersson et al.
1994). A QTL for growth was also found on chromosome 13 accounting
for 7-12% of the phenotypic variation. Additional confirmation
of the chromosome 4 results have been seen in subsequent generations
(Marklund et al. 1996b) and by other experiments using
Chinese pig crosses (Wang et al. 1997a; Milan et al.,
1998; Moser and Cepica, personal communication). Using a candidate
gene analysis PIT1 was identified to be associated with
backfat and birth weight (Yu et al. 1995) and it maps in
the center of the chromosome 13 QTL found by Andersson et al.
(1994). Chromosome 13 QTL have also been identified for 21 and
35 day weights in Wild Boar by Pietran crosses in the region of
PIT1 (Moser, personal communication). Efforts are underway
to resolve whether the chromosome effect is due to PIT1 or to
another gene in the region (Yu et al. 1997).
The pig major histocompatibility complex (MHC) spans the centromere
of chromosome 7. Associations between MHC haplotypes and several
traits have been reported over the years. These have been confirmed,
in part, using MHC class I DNA probes (Jung et al. 1989).
More recently, QTL scans have identified QTL for growth and backfat
traits in Chinese crosses on chromosome 7 (Rothschild et al.
1995; Bidanel et al. 1996; Chevalet et al. 1996;
Moser et al. 1997; Wang et al. 1997b). The backfat
and birth weight QTL centered near the region of TNFA and
S0102. A candidate gene analysis involving AMPEPN,
which maps to the same region, also revealed an association with
growth rate (Nielsen et al. 1996). The overall results
to date suggest that at least one growth and backfat QTL exists
in this region. Other results have included a growth trait QTL
on chromosome 6, but it seems to be associated with the known
effect caused by the RYR1 gene causing malignant hyperthermia
(Geldermann et al. 1996) or other unknown genes in the
immediate vicinity of RYR1. Some additional associations
have been reported for chromosome 3 (Casas-Carrillo et al.
1997b), chromosomes 6 and 8 (Wilkie et al. 1996) and chromosome
14 in a limited QTL scan (Bidanel et al. 1996).
A combination of QTL scans and candidate gene analyses using GH
have been performed for chromosome 12 for several performance
measures (Nielsen et al. 1995; Casas-Carrillo et al.
1997a; Knorr et al. 1997) but results were not in general
agreement. Analysis of the chromosome 5 region near IGF-1
revealed significant effects on average daily gain (Casas-Carrillo
et al. 1997a). Additionally, Gerbens et al. (1997)
and Tepas et al. (1996) reported associations of the heart
fatty acid-binding protein (H-FABP) and the myogenin genes
with average daily gain. Other candidate genes including leptin,
CCK and CCKAR (Clutter et al. 1996) and leptin
receptor (Vincent et al. 1997) have been mapped and may
prove to be associated with growth, fatness and appetite traits.
It has been known for some time that pale soft and exudative (PSE)
pork is caused by the RYR1 gene on chromosome 6. This
has been well demonstrated in a QTL scan for several meat quality
traits related to PSE in an F2 population originating from a Pietran
background (Geldermann et al. 1996). Focus has also centered
on a gene originating in Hampshires called the RN gene
which is associated with lower pH and increased gycogen content
in the meat. The RN gene has now been mapped to chromosome
15 (Milan et al. 1996; Mariani et al. 1996a; Reinsch
et al. 1997) and surrounded by flanking markers. The actual
gene has alluded researchers, but a recent report suggests that
a DNA test for the RN gene has been found by PIC researchers
(De Vries et al. 1997). Andersson and colleagues (Andersson-Eklund
et al. 1996) have conducted one of the most complete QTL
scans for meat quality using 234 markers on 191 F2 animals. QTL
for several meat quality traits (pH, water holding capacity and
pigmentation) were found to be on chromosome 2 and chromosome
12. Rothschild and colleagues report some association of meat
color and firmness scores with regions on chromosomes 4 and 7
(Rothschild et al. 1995, Wang et al. 1997a; Wang
et al. 1997b). Additional associations with meat quality
traits have been reported for chromosome 7 (Moser et al. 1997)
and for number of muscle fibers on chromosome 3 (Milan et al.,
1998). Two other interesting associations related to meat quality
have been noted for chromosome 7. The activity of Malic enzyme,
a lipogenic enzyme in muscle has been shown to be associated with
the SLA complex on chromosome 7 (Renard et al. 1996).
Furthermore, a directed QTL scan revealed that there was a major
QTL for androstenone level which is associated with boar taint
in the region of the SLA complex (Bidanel et al. 1996;
Milan et al., 1998).
Among candidate genes investigated for muscle quality is the H-FABP
gene which may be associated with intramuscular fat (Gerbens et
al. 1997). Other genes mapped and investigated include myogenin
(Tepas et al. 1996) and calpastatin (Ernst et al.
1997). Coat color, though not directly associated with meat quality
is of interest to the packing industry. White pigs are preferred
at slaughter and the cost of a "colored carcass" at
some locations may be over $1/pig. Andersson and colleagues (Johansson-Moller
et al. 1996) have now identified the KIT gene as
that responsible for white coat color and a DNA test is patented
and being used in MAS programs (Andersson and Plastow, personal
communication). The MSHR gene has also been identified
to control red and black color in the pig (Mariani et al.
Given the necessity of larger resource families and the difficulty
and time required to obtain information on reproduction traits,
it is not surprising that results of QTL scans for these traits
are limited. Initial scans have revealed promising results on
chromosome 8. Wilkie et al. (1996) reported possible QTL
for uterine length and ovulation rate, though in different chromosomal
positions. Rathje et al. reported a sizable QTL for ovulation
rate (+3.07 ova) on chromosome 8 also but some distance from the
ovulation QTL observed by Wilkie and colleagues. In the French
QTL experiment (Milan et al., 1998) a QTL for increased
litter size of one piglet was found in the same location on chromosome
8 as Rathje. The large ovulation rate/litter size QTL on chromosome
8 is of interest as it mapped to the region which is syntenic
to the Booroola fecundity gene in sheep. Interestingly, using
a single microsatellite marker (OPN) in the same chromosome
8 region, Short et al. (1997b) also found significant effects
for litter size in commercial line. Limited chromosome QTL analyses
have further suggested other reproductive QTL on chromosomes 4
and 6 (Wilkie et al. 1996), on chromosome 7 (Wilkie et
al., 1996; Milan et al., 1998) and chromosomes 4, 13, 15
(Rathje et al. 1997). Both Rathje et al. (1997)
and Bidanel et al. (1996) have enlarged their experiments
which can be expected to yield additional useful results.
Candidate gene analysis for reproduction has shown considerable
merit. Results have clearly demonstrated that the estrogen receptor
(ESR) is significantly associated with litter size (Rothschild
et al. 1996; Short et al. 1997a). Estimates of
allelic effects vary from 1.15 pig/litter in Meishan synthetics
to .42 pigs/litter in Large White lines. These results have not
been confirmed by QTL scans using divergent crosses involving
Meishan and Large White pigs. This may have resulted from small
sample sizes or the fact that the ESR B allele was in both
parental populations involved in the QTL scan and it was not specifically
genotyped in those experiments. Other effects have been reported
for retinoic acid receptor gamma (RARG), retinol binding
protein 4 (RBP4), and melatonin receptor 1A (MTNRIA)
genes (Messer et al. 1996; Ollivier et al. 1997).
More recent results have demonstrated that the prolactin receptor
(PRLR) locus is significantly associated with litter size
(Vincent et al. 1998). Most of the candidate gene analyses
have involved considerably more sows and litters than the QTL
analyses and this might explain the lack of QTL scan confirmation
of the regions in which the candidate gene effects have been reported
To date, QTL scans for disease resistance or immune response QTL
have been limited. An exception is work underway by Andersson
and colleagues (Edfors-Lilja and Andersson, personal communication)
to study some immune response parameters. Some immune capacity
QTL have been identified. Also, a QTL for base cortisol level
which may be related to stress and perhaps immune response, has
been mapped to the end of chromosome 7 (Milan et al., 1998).
Analyses of associations of candidate genes have been more substantial.
The general location of the K88 E. coli receptor has
been known for some time and fine mapping and candidate gene analysis
of the region is underway in many labs. Two alpha (1,2) fucosyltransferase
genes (FUT1, FUT2) on porcine chromosome 6q11 have
been identified and are closely linked to the blood group inhibitor
(S) and Escherichia coli F18 receptor (ECF18R) loci
(Vögeli, personal communication). Vögeli and colleagues
have found a polymorphism which is closely linked to ECF18R
in Large White, Landrace, Hampshire, Duroc and Pietrain pigs and
it could be a good marker for marker assisted selection of
E. coli F18 adhesion resistant animals in these breeds. Whether
the FUT1 or FUT2 gene products are involved in the
synthesis of carbohydrate structures responsible for bacterial
adhesion remains to be determined. The SLA complex on chromosome
7 has recently been associated with resistance to primary infections
with Trichinella spiralis but not to resistance to toxoplasmosis
(Lunney, personal communication). The gene for Natural Resistance
Associated Macrophage Protein 1 (NRAMP1), associated with
resistance to Salmonella challenge in mice, has been recently
mapped to pig chromosome 15 (Sun and Tuggle, personal communication).
Several other candidate genes are being investigated. Genes associated
with human disorders, which have been identified and mapped in
the pig, include clotting factor IX (Signer et al. 1996)
and the familial hypercholesterolaemia gene (Hasler-Rapacz et
In addition to more extensive scans of existing populations, many
new QTL experiments are underway for performance, reproduction
and meat quality traits (Moran, personal communication; Rohrer,
personal communication; Rothschild, personal communication; Nezer
et al. 1996; van Oers et al. 1996). In the short
time it has taken to build a considerable genetic map, several
QTL and candidate analyses have yielded interesting results.
The QTL scans have identified several chromosomes that are now
targets for further confirmation of the chromosomal region, advanced
fine mapping of the QTL, and positional comparative candidate
gene analysis. Additional experiments will either confirm the
regions and lead to the eventual isolation of the gene or genes
of interest or will produce conflicting results. Such conflicting
results may be the results of haplotype effects, epistasis or
background genotype effects, or sampling. Given that we wish
to detect not only large but also moderate gene effects, experimental
size will need to be increased or several experimental results
will need to be pooled. At present, several PiGMaP participants
are pooling information on chromosome 4 to obtain additional power
in the analysis (C. Haley, personal communication). One approach
suggested (Janss et al. 1997) is to conduct segregation
analyses in some populations as a first stage prior to molecular
QTL scans. The QTL experiments to study disease resistance are
still lacking though candidate gene analysis using information
from human studies will be quite useful. The relevance of results
found in crosses involving the Wild Boar and the Chinese breeds
will also have to be evaluated in commercial lines. Several companies
are already attempting to use their specialized lines for such
Several quantitative trait loci scans and candidate gene analyses
have identified important chromosomal regions and major genes
associated with traits of economic interest in the pig. These
include chromosomal regions for growth and backfat (chromosomes
3, 4, 5, 6, 7, 8, 13, 14), meat quality traits (chromosomes 2,
3, 4, 6, 7, 12, 15) and reproduction (chromosome 4, 6, 7, 8).
Candidate genes for litter size (ESR, PRLR), disease
resistance (FUT1, SLA, NRAMP), and coat color
(KIT, MSHR) have also been identified. At present,
the industry is already using some of the resulting information
for DNA tests and marker assisted selection (MAS).
The author apologizes for any research inadvertently not included
in this review and gratefully acknowledges the many colleagues
around the world who kindly provided information in both published
and unpublished forms for inclusion in this review. The invitation
to speak at this conference is appreciated. Support for the gene
mapping and QTL research and activities was provided by the Iowa
Agriculture and Home Economics Experiment Station, the USDA-CSREES
Pig Genome Coordination program, BRDC, Dalgety, PIC, IPPA, NPPC
and in collaboration with the EEC PiGMaP program.
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