Beta-2-microglobulin haplotypes in U.S. beef cattle and
association with failure of passive transfer in newborn calves
Michael L. Clawson, Michael P. Heaton, Carol G. Chitko-McKown, James M. Fox,
Timothy P.L. Smith, Warren M. Snelling, John W. Keele, William W. Laegreid
United States Department of Agriculture, Agricultural Research Service, U.S. Meat Animal Research Center (MARC), Spur 18D,
P.O. Box 166, Clay Center, Nebraska 68933, USA
Received: 23 July 2003 / Accepted: 29 October 2003
Failure of passive transfer (FPT) is a condition in
which neonates do not acquire protective serum
levels of maternal antibodies. A principal compo-
nent of antibody transport is the neonatal receptor
for the Fc portion of immunoglobulin, a heterodimer
of a MHC-1 alpha-chain homolog (FCGRT) and beta-
2-microglobulin (B2M). Previously, two FCGRT
haplotypes were associated with differences in im-
munoglobulin G (IgG) passive transfer in cattle
(Laegreid et al. (2002) Mamm Genome 13, 704–710).
The present study had two objectives: ﬁrst, to char-
acterize the B2M haplotype structure in a diverse
group of U.S. beef cattle, and second, to evaluate
those haplotypes for association with either high or
low serum IgG levels in newborn calves. Twelve
single nucleotide polymorphisms (SNPs), assorted
into eight haplotypes, were identiﬁed by sequencing
regions of B2M exons II and IV in a multi-breed panel
of 96 beef cattle. Calves homozygous for one of the
eight haplotypes (B2M 2,2) were at increased risk of
FPT (odds ratio = 10.60, CI
2.07–54.24, p = 0.005).
These results indicate that this haplotype is in
linkage disequilibrium with genetic risk factors af-
fecting passive transfer of IgG in beef calves, an
important determinant of neonatal calf morbidity
Placental transfer of immunoglobulin does not occur
in cattle (Smith and Little 1922; Mikulska et al.
2000). Calves obtain maternal antibodies solely from
colostrum, the immunoglobulin G (IgG) and protein-
rich milk produced near parturition (Butler 1974;
Stott et al. 1976, 1979a). Maternal IgG is transported
across the neonatal intestinal epithelium within the
ﬁrst 24 h of life, travels through the lymphatics, and
enters blood circulation via the thoracic duct (Blood
and Radostits 1989; Besser and Gay 1994). Failure of
passive transfer (FPT) results from the reduced
transfer of IgG to neonatal serum.
A number of factors contribute to FPT, including
seasonality (Gay et al. 1965, 1983; McEwan et al.
1970), time of colostrum ingestion after birth (Stott
et al. 1979b), prolonged birth (Szenei 1983; Besser
et al. 1990; Weaver et al. 2000), housing conditions
(with or without dam) (Stott et al. 1979c), and ge-
netics (Norman et al. 1981; Muggli et al. 1987; Vann
et al. 1995; Laegreid et al. 2002). Calves affected with
FPT have increased morbidity and mortality rates
(Wittum and Perino 1995). Thus, FPT represents a
signiﬁcant risk to the health of calves.
In mammals, the neonatal receptor for the Fc
portion of IgG (FcRn) has prominent maternal and
neonatal roles in IgG transfer. In neonatal rodents,
evidence suggests that FcRn binds IgG on the lumi-
nal plasma membrane of intestinal epithelium and
mediates the transcytosis of IgG to the basolateral
surface (Rodewald and Kraehenbuhl 1984; Israel et al.
1995). In murine lactating mammary glands, FcRn
appears to function as a recycling receptor trans-
porting IgG away from the milk glands (Cianga et al.
1999). In sheep, immunohistological evidence sug-
gests that FcRn is differentially localized in mam-
mary acinar epithelial cells before and after
parturition (Mayer et al. 2002). In cattle, expression of
FcRn genes has been detected in lactating mammary
glands (Adamski et al. 2000; Kacskovics et al. 2000).
In bovine neonates, IgG and other constituents of
colostrum are transported across the intestine by
nonselective pinocytosis (Besser and Gay 1985).
DOI: 10.1007/s00335-003-2320-x • Volume 15, 227–236 (2004) •ÓSpringer-Verlag New York, Inc. 2004
Correspondence to: M.L. Clawson; E-mail: firstname.lastname@example.org.