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  • Livestock Research Station/ Assam Agricultural University (AAU)/Mondira /Hekra /Kamrup ( Assam)


Most common economically important milk constituents traits include fat, protein, SNF, lactose and ash. These characteristics and associated benefits have made milk an important part of the diet. Amongst the milk constituents, betacasein has gained importance and popularity amongst the health conscious people due to its recent health related issues. Beta casein composition of milk and milk products has become an important economic trait of dairy animals. Our indigenous dairy animals produce A2 milk and India is endowed with rich A2 dairy animals since our civilizations, protecting the masses from ill effects of A1 milk. It is a matter of great concern for the health of people in India. There is a urgent need to go through our breeding policies to stop producing A1 milk.
I.J.S.N., VOL.7 (1) 2016: 01-05 ISSN 2229 6441
Review Article
1Prasanta Boro, 2Binoy Chandra Naha, 3Deep Prakash Saikia & 4Chandra Prakash
ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P-243122
1PhD Scholar, LPM Section, ICAR-IVRI
2PhD Scholar, Animal Genetics Division, ICAR-IVRI
3PhD Scholar, Veterinary Biotechnology Division, ICAR-IVRI
4MVSc Scholar, Animal Genetics Division, ICAR-IVRI
*Corresponding author email:
Most common economically important milk constituents traits include fat, protein, SNF, lactose and ash. These
characteristics and associated benefits have made milk an important part of the diet. Amongst the milk constituents, beta-
casein has gained importance and popularity amongst the health conscious people due to its recent health related issues.
Beta casein composition of milk and milk products has become an important economic trait of dairy animals. Our
indigenous dairy animals produce A2 milk and India is endowed with rich A2 dairy animals since our civilizations,
protecting the masses from ill effects of A1 milk. It is a matter of great concern for the health of people in India. There i s a
urgent need to go through our breeding policies to stop producing A1 milk.
KEYWORDS:A1 and A2 Milk, Human health
Milk is the complete food for the infant. It contains the
essential micro-nutrients needed for growth and
development of human health as well as for the neonate
animal. In USA, Australia, New Zealand and other
developed countries, people use to consume milk
according to their needs and use milk like A2 milk, since
A2 milk is harmless whereas A1 milk is harmful for
health. So, our future breeding policies for dairy animals
should be done in a systematic manner, keeping an eye on
producing clean and healthy milk which is none other than
A2 Milk.
What actually is A1 and A2 milk?
Milk contains about 85% water. The remaining 15% is the
milk sugar lactose, protein, fat and minerals. Beta-casein is
about 30% of the total protein content in milk. A2 milk is
the milk that contains only the A2 type of beta-casein
protein whereas A1 milk contains only A1 beta casein or
A1A2 type variant. A1 protein variant is commonly found
in milk from crossbred and European breeds of cattle. A2
milk is found basically in indigenous cows and buffaloes
of India (Asia as a whole). A2 milk is branded by the A2
Milk Company like A2 Corporation and sold mostly in
Australia, New Zealand, United Kingdom and other
developed countries.
History of A1 and A2 Milk
A2 beta-casein is the beta-casein from cows that have been
produced since before they were first domesticated over
10,000 years ago. It has no known negative effects on
human health. In the past few thousand years, a natural
mutation occurred which has resulted in a proportion of
cows of European breeds producing a casein variant called
A1 beta-casein. Slowly, these protein variant became
dominant in milk which producing A1 milk. The gene
encoding beta-casein was changed such that the 67th
amino acid in the 209 amino proteins was switched from
proline to histidine. This new kind of beta-casein that was
created is known as A1 beta-casein which is found in the
milk of many crossbred cows such as Holstein, jersey and
Basic genetics of A1 and A2 milk
The A1/A2 status of a cow is determined by a pair of
genes on the sixth chromosome (Rijnkels, 2002). There
are two major alleles of the gene i.e A1 and A2 beta-
casein alleles. A cow carries two copies of the beta-casein
gene; she can carry either of A2A2 (homozygous), A1A2
(heterozygous) or A1A1 (homozygous) alleles. Neither
allele is dominant over the other rather; they are co-
dominant i.e. additive in their effect. Therefore, an A1A2
cow will produce A1 and A2 beta-casein in equal
amounts. An A2A2 cow will only produce A2 beta-casein
and an A1A1 cow will only produce A1 beta-casein. The
Northern European breeds of cows such as the Friesian
and Holstein carry the A1 and A2 allele at about equal
levels. The Southern European breeds and the Jersey carry
the A1 allele at about 35% and 2/3 of A2. Exceptionally,
Guernsey breed appears to carry the A1 allele at less than
10% and the Scottish Ayrshire breed appears to be well
over 50%. In addition, individual herds may carry the
allele at levels that are quite different to the average for the
breed. If a cow is A2A2 then she is guaranteed to pass on
the A2 allele to her progeny. Similarly, an A1 cow is
guaranteed to pass on the A1 allele. For an A1A2 cow
there is a 50% chance of passing on either of the allele.
Status of Milk protein variants in Cattle
Researches conducted on indigenous cows (Zebu type),
buffaloes and exotic cows (Taurine type) have revealed
A1 and A2 Milk: Its impact on human health
that A1 allele is more frequent in exotic cattle (A1 milk)
while Indian native dairy cows and buffaloes have only A2
allele and hence are a source for safe milk i.e A2 milk
(Mishra et al., 2009). The A2 allele gene in Indian milk
breeds of cows and buffaloes are 100% (Red Sindhi,
Sahiwal, Tharparkar, Gir and Rathi), other Indian breeds
used for farming, is around 94 per cent (Joshi, 2011) and
while in foreign breeds (HF and Jersey), it is around 60
per cent (NBAGR, 2011). A1 β-casein is absent in the
milk of pure Asian and African Cattle (Ng-Kwai-Hang
and Grosclaude, 2002). So, our indigenous cows and
buffaloes produce A2 milk.
1. Allelic and genotypic frequency of Beta casein gene across the Indian cattle breeds (Mishra et al., 2009)
Sl. No.
Cattle breeds
Allelic Frequency
Genotype Frequency
Red Sindhi
Red Kandhari
Malnad Gidda
2. Occurance of Beta casein gene variants in various cattle breeds and countries (Kaminiski et al., 2007)
Sl. No.
Cattle breeds
Frequency of Beta casein alleles
Ehrmann et al., 1997
Bech et al., 1990
New Zealand
Winkelman and
Wickham, 1997
Enennam et al.,1991
Lien et al., 1993
Swaissgood, 1992
Brown Swedish
Ehrmann et al., 1997
Curik et al.,1997
Swaissgood, 1992
3. Allelic and genotypic frequency of Beta casein gene across the Indian Buffalo breeds (Mishra et al., 2009)
Sl. No.
Buffalo breeds
Allelic Frequency
Genotype Frequency
South Kanara
Assamese Swamp
Milk protein and BCMs
Bovine milk protein is composed approximately of 80%
casein and 20% whey (Shah, 2000; Niki et al., 1994;
Martien et al., 1994). But according to some researchers
whey proteins constitute about 14% (McLachlan, 2001;
Roginski, 2003). It contains four components namely αs1
(CSN1S1, 3946%), αs2 (CSN1S2, 811%), β(CSN2,
2535%), and κ(CSN3, 815%) of total caseins (Eigel et
al., 1984; Roginski, 2003,Rijnkels, 2002)whereas human
milk casein is composed of primarily β, and κ1.β-casein
is the second most abundant protein and crucial for casein
micelle structure. Beta-casein is 30% of the total protein
content in cow's milk. The polymorphic status of bovine β-
casein is confirmed, and till date 13 allelic variants have
been identified (Kaminski et al., 2007). Amongst these,
A1 and A2 variants are reported to be the most common
allelic variants of β-casein in dairy cattle (Farrell et al.,
2004). The polymorphic nature and its association with
I.J.S.N., VOL.7 (1) 2016: 01-05 ISSN 2229 6441
milk, fat and protein yield attracted several efforts in
evaluating this locus as a potential dairy trait marker
(Ikonen et al., 1999; Caroli et al., 2004; Kucerova et al.,
2006). Consumption of milk of certain breeds of cow,
buffaloes, sheep and goat may result in the release and
possible absorption of bioactive peptides like BCMs.
These peptides yielded by the digestion of β-casein have
opioid effects similar to morphine, and so named β-
casomorphins (β-CMs). The β-CMs have unique structural
structural features that impart a high and physiologically
significant affinity with the binding sites of endogenous
opioid receptors (Meisel and FitzGerald, 2000). Of the
protein variants A1 betacasein yields BCM-7 whereas A2
betacasein does not give rise to BCM-7 upon digestion
(Woodford, 2006; Bell et al., 2006). β-CM-7 has been well
established as a potent bio-active peptide with opioid
Mechanism of BCM-7 generation in the Small intestine
The A1 and A2 variants of bovine β-casein differ at amino
acid position 67 with histidine in A1 and proline in A2
milk. This polymorphism leads to key conformational
changes in the secondary structure of expressed β-casein
protein (Elliot et al., 1999; McLachlan, 2001). Due to
presence of histidine at amino acid 67 position, digestion
of A1 β-casein milk releases a 7 amino acid bioactive
peptide called beta-casomorphin 7 (BCM-7) in small
intestine, while proline in A2 milk at 67 position prevents
the split at this particular site and generates peptide BCM-
9 (Roginski, 2003; Kostya et al., 2004). It is believed that
generation of BCM-7 is the major causative factor
associated with A1 milk related health disorders.
However, A2 β-casein not been linked to any of such
health issues (Kaminski et al., 2007).
Impact of A1 and A2 milk on human health
Milk from dairy cows is providing a high quality source of
protein and an essential micronutrients like energy,
calcium, magnesium and phosphorus to human beings
since long time (Bell et al., 2006). A significant
relationship was observed between bovine milk protein
consumption and the incidence of type 1 diabetes and
CVD (McLachlan, 2001; Laugesen and Elliott, 2003;
Elliott et al., 1999; Thorsdottir et al., 2000, Virtanen et al.,
2000; Monetini et al., 2002; Birgisdottir et al., 2002),
arteriosclerosis (Tailford et al., 2003). Besides,
neurological disorders such as schizophrenia and autism
(Woodford, 2006), and sudden infant death syndrome
were also appeared to be known to potentiated by milk
(Sun et al., 1999; Sun and Cade, 1999; Sun et al., 2003).
The relationship between disease risk and bovine milk
consumption is the focus of this review with special
emphasis to A1 and A2 hypothesis.
In many of the medical literature we get to know the link
between the development of ischemic heart disease (CVD)
and specific milk protein intake (McLachlan, 2001;
Laugesen and Elliott, 2003; Tailford et al., 2003). Besides,
some populations such as the Masai (East African) and
Samburu (Northern Keyan) had virtually no heart disease
despite consuming a diet rich in animal milk. But that milk
fortunately came from Zebu cattle, which is a breed that
carries the A2 allele exclusively (McLachlan, 2001).
Western countries, which had similarly high bovine milk
consumption from predominantly the Holstein breed,
jersey and other breeds had a greater incidence of CVD
than nations with low milk consumption. It is so because
people of small nations consume fortunately A2 milk. But
epidemiological analyses concerning the two alleles of β-
casein and the incidence of CVD underscores the apparent
relationship between the risk of chronic disease and milk
protein variant intake (McLachlan, 2001; Laugesen and
Elliott, 2003). Above all many researchers have claimed
the relationship of A1 milk with many human diseases like
CVD, autism, schizophrenia etc (Woodford, 2011, Mishra
et al., 2009).
The Food and Agriculture Organisation (FAO) (2012) has
reported increase in many chronic diseases arising out of
milk. These diseases if studied thoroughly can be
alleviated by improving the health benefiting milk
components. The β-casein composition of the protein
fraction has become of special interest recently because of
a possible relationship between β-casein genotype and the
health of population of consumers. Genetic variants in
bovine β-casein gene (A1 and B) release a bioactive
peptide, β-casomorphin-7(BCM-7) upon digestion,
responsible for many human disorders like Type 1
diabetes, autism, schizophrenia and heart diseases but A2
milk does not cause such type of illnesses (Keith
Woodford, 2007; Mishra et al., 2009; Sodhi et al., 2012).
Infants may absorb β-CM-7 due to an immature
gastrointestinal tract. Adults, on the other hand, appear to
reap the biological activity locally on the intestinal brush
boarder. Β-CM-7 can potentially affect numerous opioid
receptors in the nervous, endocrine, and immune systems.
Whether there is a definite health benefit to milk
containing the A2 genetic variant is unknown and requires
further investigation unlike harmful effects of A1 milk.
With the increasing intake of dairy products, the
consumption of other essential nutrients such as zinc,
vitamin A, magnesium, folate, and riboflavin are also
increasing (Weinberg et al., 2004). However, we are able
to get only about 700 mg of calcium per day, which comes
primarily from dairy products (Weinberg et al., 2004;
Ervin et al., 2004). This amount is against the
recommended amount of 1,0001,500 mg (NIH
Consensus Development Conference, 1994). Most other
food sources contain low concentrations of calcium.
Calcium content of milk, may reduce the risk of
osteoporosis and colon cancer (Heaney et al., 1999; Birt et
al., 1999) and including milk in the diet may promote
weight loss (Phelan et al., 2003). The ideal calcium to
magnesium ratio for the human body should be 2:1. The
A1 milk's ratio is 10:1. By relying on A1 cow's milk for
calcium, we will have magnesium deficiency and
imbalance, but A2 milk does not cause such imbalances.
Magnesium relaxes us, helps improve digestion, is anti-
inflammatory in action, involved in nerve and muscle
function, de-toxifier, increases alkalinity of the blood and
flexibility of the tissues. Magnesium is required for the
body to produce and store energy. Without magnesium
there is no energy, no movement, no life. So, A1 milk will
lower magnesium levels whereas A2 milk does not.
The inflammation from A1 milk casein causes lymphatic
congestion and metabolic suppression. A1 milk worsens
acne, eczema, upper respiratory infections, asthma and
allergies. It causes digestive problems, not because of the
lactose but because of massive histamine release from
casomorphin. Ear infections, bronchitis, tonsillitis are
A1 and A2 Milk: Its impact on human health
driven by A1 casein. A1 milk casein causes endometriosis
because of its inflammatory and immune-disruptive effect.
Endometriosis is a gynecological condition in which cells
from the lining of the uterus (endometrium) appear and
flourish outside the uterine cavity, most commonly on the
membrane which lines the abdominal cavity. Many
women with infertility may suffer from endometriosis and
other reproductive complications.
We can now conclude that we should drink A2 milk only
as it prevents us from milk related health complications
especially from A1 milk. More research is also required to
prove the reality of the hypothesis of A1 and A2 milk. In
this aspect, Government’s support is needed to accomplish
the above anomalies of milk quality and standards to
improve the health of the people.
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... Several studies have indicated that milk protein genes are associated with the quantitative and qualitative aspects of milk production [19][20][21] and health-related issues in the consumer community. [22][23][24] In addition, milk protein variants have been used to characterize breeds, 25 investigate biodiversity, 26 and conduct evolution experiments on both animal resources and milk protein genes. 27,28 The casein genes are closely linked and inherited as a cluster so they are considered as a potential target for marker-assisted selection for milk production traits. ...
... Similarly, in the Nili-Ravi buffaloes, the PCR sequence data of the CSN2 gene was compared with reference sequence Bubalus bubalis (NC_037551.1) and only a single SNP was identified at position 20495 present in the intron region between exon-6 and exon-7 (Table 2). Moreover, allele-specific primers 23 showed the presence of the A2 allele in all Sahiwal and Nili-Ravi animals. ...
Full-text available
Milk protein genes are associated with milk yield and composition in dairy animals. The present study aimed to identify milk protein genes (CSN1S1, CSN2, CSN3, and BLG) genetic variants and their association with milk yield in Sahiwal cattle and Nili-Ravi buffaloes. One hundred animals from each species were selected to collect blood samples and milk production records. Primers were designed for these milk protein genes for PCR amplification. Sequencing of resultant PCR products revealed a higher number of SNPs (13 vs. 7, 5 vs. 1, and 6 vs. 2) in Sahiwal as compared to Nili-Ravi animals in CSN1S1, CSN2, and CSN3 genes, respectively. However, a single SNP was observed in BLG gene of both species. Association analysis revealed that one SNP in BLG gene of Nili-Ravi was associated (p < 0.05) with 305-day milk yield. Two SNPs at CSN1S1 gene in Sahiwal were associated with dry-period. Similarly, one SNP at CSN1S1 and two SNPs at CSN3 gene showed significant association (p < 0.05) with average calving-interval in Sahiwal while two SNPs in CSN1S1 gene were associated (p < 0.05) with this trait in Nili-Ravi. These SNPs could be helpful as candidate variants for marker-assisted selection in cattle and buffaloes for improvement of lactation performance.
... The ideal calcium to magnesium ratio in the human body should be 2:1 whereas A1 milk has a higher ratio in the range 10:1. This can lead to magnesium deficiency in humans (Boro et al., 2016). ...
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Background: Majority of the people believed that, only the native breeds have A2 milk than exotic or crossbred animals. There is no enough research on milk protein variants have been carried out in Indian zebu cattle. Present study was conducted to screen more number of crossbred cattles and buffaloes in Tamil Nadu to identify the frequency of A1 and A2 alleles in the population.Methods: The study was conducted on 68 cattle and 172 murrah / graded murrah buffaloes to explore the polymorphic variants of β-casein gene. Genomic DNA was extracted by phenol-chloroform method. Polymerase Chain Reaction (PCR) was performed with allele specific primers to amplify a 244 bp long fragment of beta-casein gene and visualized in 2% agarose gel electrophoresis. The population genetic indices were calculated based on the formulas.Result: In the present study revealed higher level of A2A2 genotype frequency (1.00) and fixation of A2 allele in kangayam cattle and murrah / graded murrah buffalo. The observed frequency of A1A1, A1A2 and A2A2 genotypes were 0.38,0.62 and 0.00 for jersey crossbred and 0.29, 0.71 and 0.00 for HF crossbred cattle. The range of Expected homozygosity (0.50 to 1.00), polymorphism information content (0.30 to 0.38), effective number of alleles (1.00 to 2.00) and level of possible variability realization value (44.54% to 100%) reflected existence of medium genetic variability in studied population.
... The present study gave the evidence that even Nepalese taurine cattle, Lulu cattle, exhibited A2 variant of beta-casein while globally most of the taurine population such as Red (0.710) cattle, Ayrshire (0.432-0.720) and Holstein-Friesian (0.310-0.660) are predominantly with A1 variant. Nevertheless, Guernsey (0.880-0.970) and Jersey (0.490-0.721) cattle have a high frequency of A2 (Boro et al 2016). The milk yield corresponds with the A1 variant of beta casein. ...
... The present study gave the evidence that even Nepalese taurine cattle, Lulu cattle, exhibited A2 variant of beta-casein while globally most of the taurine population such as Red (0.710) cattle, Ayrshire (0.432-0.720) and Holstein-Friesian (0.310-0.660) are predominantly with A1 variant. Nevertheless, Guernsey (0.880-0.970) and Jersey (0.490-0.721) cattle have a high frequency of A2 (Boro et al 2016). The milk yield corresponds with the A1 variant of beta casein. ...
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Indigenous chickens are quite popular in Family Poultry Production System (FPPS) in Nepal, but are constrained with their low productive performance. The present study evaluated the productive and reproductive performance of Sakini chicken in different filial generations and sexes. In addition, research also aimed at understanding the effect of generations on above performances. Initially, base populations (G-0) of Sakini were maintained by collecting eight weeks old birds from different agro-ecologial zones of Nepal. Performance of the birds of G-0 was evaluated based on weekly body weight (12-24 weeks), laying performance, fertility, hatchability, hatch weight and survivability. Selected birds of base population (G-0) were used to produce first (G-1), second (G-2) and third (G-3) generations through selective breeding in each generation. Similarly, body weights at hatching, 12 weeks, 16 weeks, 20 week and 24 weeks were significantly (p<0.001) improved from G0 to G3 and were also significantly (p<0.001) differ for sex (males were always heavier than females). Likewise, there was significant (p<0.05) improvement in egg production (per hen per year), age at first lay (days), body weight at sexual maturity, egg number and egg weight at 90 days of laying in progressive generations. Fertility, hatchability and survivability significantly (p<0.05) improved in selected generations in comparison to base population, whereas, no significant difference was obtained within the different selected population. Thus, indigenous Sakini chicken under this experiment performed better with respect to survivability, fertility and hatchability in later generations that provides ample scope of advancing selective breeding activities within the indigenous population in order to bring significant improvement in the overall productive performance of Sakini chicken in Nepal.
... The present study gave the evidence that even Nepalese taurine cattle, Lulu cattle, exhibited A2 variant of beta-casein while globally most of the taurine population such as Red (0.710) cattle, Ayrshire (0.432-0.720) and Holstein-Friesian (0.310-0.660) are predominantly with A1 variant. Nevertheless, Guernsey (0.880-0.970) and Jersey (0.490-0.721) cattle have a high frequency of A2 (Boro et al 2016). The milk yield corresponds with the A1 variant of beta casein. ...
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Lulu is an indigenous breed of cattle (Bos taurus) found in high altitude regions of western Nepal. Population of Lulu cattle has been declining due to introgression with other exotic breeds to increase milk productivity. Here we aimed at finding potential approach for conserving Lulu cattle and its assets by studying the milk contents and investigating which variant of beta-casein protein is present in this breed. Beta caseins are an abundant protein in cow milk with A1 and A2 being the most common genetic variants of this protein. Consumption of A1 type of milk has numerous health-related complications whereas A2 type of milk has numerous human health promoting factors. We used restriction fragment length polymorphism (RFLP) for determining the A1 and A2 variant of beta casein in Lulu cattle. For performing DNA extraction, we collected (n = 18) blood samples of Lulu from Mustang and (n=17) Nepal Agriculture research council farm. The amplified fragments in 3% agarose at 251bp and 213bp respectively confirmed the presence of both A1 and A2 gene in Lulu; however, A2 was of greater abundance. Our study indicated that Lulu has A2 variant of beta-casein predominantly. The gene frequency of A1A1 is 0, A1A2 is 0.06 and A2A2 is 0.94. We further found that the allele frequency of A1 and A2 is 0.03 and 0.97 respectively. We designed special primer for sequencing CSN2 genes since A2 type beta casein gene was predominantly seen on Lulu. The sequencing result further supports our RFLP result as most of our samples have “C” nucleotide SNP in amplified CSN2 gene sequence. The Chi-square value of the current study is 0.04 which supports Hardy-Weinberg equilibrium inferring that Lulu cattle are still in the pure state, where there is no genetic introgression with the exotic breed for the sake of improvement of productivity.
... Each Cn gene has several variants, which are differently distributed in the cattle breeds. The knowledge of Cn variants possessed by a cattle breed is important both from a technological point of view (quality and quantity of milk and cheese yield), and for their innate biological functions (Holt et al. 2013;Gustavsson et al. 2014;Boro et al. 2016;Ketto et al. 2017;Poulsen et al. 2017;Ozdemir et al. 2018). ...
The genetic variant A1 of bovine β-casein (β-Cn) presents a His residue at a position 67 of the mature protein. This feature makes the Ile⁶⁶-His⁶⁷ bond more vulnerable to enzymatic cleavage, determining the release of the peptide β-Cn f(60–66), named β-casomorphin 7 (BCM7). BCM7 is an opioid-agonist for μ receptors, and it has been hypothesized to be involved in the development of different non-transmissible diseases in humans. In the last decade, studies have provided additional results on the potential health impact of β-Cn A1 and BCM7. These studies, here reviewed, highlighted a relation between the consumption of β-Cn A1 (and its derivative BCM7) and the increase of inflammatory response as well as discomfort at the gastrointestinal level. Conversely, the role of BCM7 and the effects of ingestion of β-Cn A1 on the onset or worsening of other non-transmissible diseases as caused or favored by still need proof of evidence. Overall, the reviewed literature demonstrates that the “β-Cn A1/BCM7 issue” remains an intriguing but not exhaustively explained topic in human nutrition. On this basis, policies in favor of breeding for β-Cn variants not releasing BCM7 and consumption of “A1-like” milk appear not yet sound for a healthier and safer nutrition.
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La leche es un alimento esencial para los humanos y una de sus importancias radica en el contenido de proteínas lácteas. Las proteínas más frecuentes en este preciado líquido son las caseínas (αS1-caseína, αS2-caseína, β-caseína y κ-caseína), las cuales son fuente de aminoácidos para la dieta de los mamíferos en sus primeros días de vida. En la leche, las caseínas, están formadas por agregados moleculares de proteínas de tamaños variables denominados micelas. El objetivo de esta revisión es presentar un panorama general de la estructura, propiedades y genética de las caseínas lácteas y su relación con la salud humana. A partir de esta revisión, se pudo establecer, que las αs1 y αs2 caseínas se encuentran en conjunto con la β-caseína, formando el núcleo micelar, interactuando con los iones de calcio, para formar y mantener la micela estable. Animales caracterizados genéticamente con algunas variantes de estas proteínas, se asocian con un rendimiento en el volumen de leche. La κ-caseína, por su parte, está asociada con un aumento en el rendimiento y calidad de los quesos, de ahí su importancia económica, mientras que las formas más comunes de β-caseína en razas de ganado lechero son A1 y A2. La β-caseína A2 no presenta efectos negativos a la salud humana, por el contrario, ha sido asociada con propiedades reductoras de colesterol y triacilglicéridos. Sin embargo, la variante A1 de la β-caseína produce un péptido bioactivo denominado β-casomorfina-7 (BCM-7), que puede desempeñar un papel etiológico poco claro en el desarrollo de algunas enfermedades en humanos, tales como: enfermedad isquémica del corazón, diabetes mellitus tipo 1, síndrome de muerte súbita infantil (SIDS), desórdenes neurológicos, como autismo y esquizofrenia.
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The paper reviews literature data with respect to the risk of beta-casein A1 milk variant (A1 β-CN) consumption in humans and etiopathogenic mechanisms involved. This allele of β-CN particularly came into notice by the possibility of its cleavage during the digestion process, with the release at the level of the digestive system of a strong opioid named beta-casomorphin-7. This opioid is associated with pathological conditions in humans by affecting the digestive, circulatory, and nervous systems (for instance, diabetes mellitus type I, ischemic heart disease, autism, and schizophrenia). The debated topic is important for public health, but also for animal science, completing the multitude of studies focused on associations of different allelic variants within each type of casein or whey proteins with various technological properties of milk and even with certain qualitative and quantitative characteristics. This time, a potential alarm signal was debated for a more efficient selection of dairy cows for the benefit of consumer health and not only in terms of the profitability of their breeding. Although there are evidences of negative effects on human health of liberated bioactive beta-casomorphin-7, these evidences cannot be generalized and are mostly dependent on the individual reactivity.
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Milk is the ideal food for all age groups of human being. Milk consists of 87 per cent water and the remaining 13 per cent is the milk sugar lactose, protein, fat, vitamins and minerals. Casein is the chief component of the milk proteins of which about 30 per cent is beta-casein. The major beta-casein variants are A1 and A2. Beta-casein consist a chain of 229 amino acids. Cows that produce milk contain proline amino acid are called as A2 cows. A2 milk is found basically in indigenous cows and buffaloes of India. Around 5,000 years ago, a mutation occurred in this proline amino acid, converting it to histidine amino acid at 67 th position. Cows that have this mutated beta casein protein are called A1 cows. Different mutations bovine beta casein produce 13 genetic variants and out of these A1 and A2 are the most common. A1 β-casein is enzymatically broken down in the intestine to produce beta-casmorphin-7 (β-CM-7) which is an opioid peptide similar to morphine. BCM-7 interacts with the human gastrointestinal tract, internal organs and brainstem. BCM-7 adversely affects the immune response and is also considered as a risk factor for chronic heart diseases (CHD) and juvenile insulin dependent type I diabetes mellitus (DM-I). The original beta casein protein in bovine milk was A2. A2 is more comparable to the human beta casein than A1 in terms of digestive breakdown. Indigenous dairy breeds of cow (Red Sindhi, Sahiwal, Tharparkar, Gir and Rathi) and buffalo produce A2 milk and India is endowed with rich A2 dairy animals.
Milk is composed of water, proteins, lipids, lactose, vit-amins, and minerals. More than 80% of most mam-mals’ milk proteins are con-stituted by caseins. Casein is a group of proteins and they are sub-divided into αs1-, αs2-, β- and -casein families. Among these ca-sein families, -casein is the second most abundant pro-tein. Different mutations in the cow milk -casein gene led to 12 genetic variants and most common of these are genetic variants A1 and A2. The A1 and A2 variants differ only at amino acid position 67, which is histi-dine in A1 or proline in A2 milk. This difference in amino acid sequence sug-gests a conformational change in the secondary structure of the expressed β-casein. Milk that contains A1 β-casein and A2 β-casein are known as A1 milk and A2 milk, respectively. A1 β-casein milk releases an amino acid bioactive pep-tide called beta-casomorphin-7 (CM-7) in small intestine. Beta-casomorphin-7 released from A1 β-casein is respon-sible for many human dis-orders like type-1 diabetes, autism, schizophrenia, alz-heimer’s disease (AD), at-tention deficit hyperactivity disorder (ADHD), multiple sclerosis (MS) and heart diseases.
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Milk samples from 1454 first lactation heifers were collected from five breeds of cattle in a representative sampling of the California dairy cattle population. Samples were phenotyped for αs1-casein, β-casein, κ-casein, and β-lactoglobulin using PAGE. Lactation yields for milk, fat, and protein were available on 1166 heifers. Genetic linkage of the casein loci and the relationship between milk protein genotypes and production parameters (milk, fat and protein yield, fat and protein percentage) was investigated. Gene frequencies were similar to those found in other studies of the American dairy cattle population. Linkage was found between β-casein and κ-casein in four of the five breeds and between β-casein and αs1-casein in the Jersey breed. Casein haplotypes BBB and CA3A (αs1-, β-, κ-casein respectively) occurred in the Holstein population more often than would be expected from a random combination of the alleles. Least squares analysis of the production data indicated that the only significant effect was that of κ-casein genotype on protein yield; the highest yields were obtained for the BB genotype.
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This report reviews changes the nomenclature of bovine milk proteins necessitated by recent advances of our knowledge. Identification of a number of milk proteins (αs1-, β-, and κ-caseins; α-lactalbumin and β-lactoglobulin) continues to be based upon their primary structures (amino acid sequences). Since our last report, αs2-casein and serum albumin can be added to the list of major milk proteins for primary structure is known. Changes recommended in the nomenclature of caseins are primarily a result of differences within this family of proteins brought about by posttranslational modification. For example, αs0-casein is identical to αs1-casein, and αs3-, αs4-, and αs6-caseins are identical to αs2-casein except for differences in degree of phosphorylation. Additionally, proteose-peptone components 5, 8-slow and 8-fast, and γ1-, γ2-, and γ3-caseins are N-terminal and C-terminal fragments, respectively, of β-casein formed during proteolysis by plasmin. Nomenclature of immunoglobulins remains consistent with guidelines for human proteins and is based largely upon crossreactivity with reference proteins.The minor whey protein lactollin is β2-microglobulin for which the sequence of amino acids is known. An operational definition for proteins associated with the milk fat globule membrane has been developed. Nomenclature initially suggested for these proteins was based upon their electrophoretic behavior under a given set of conditions.Because of increased interest in milk proteins of species other than bovine, the Committee suggests that these be identified as homologs of those already characterized in European, Bos taurus, and Indian, Bos indicus, cattle. Guidelines are given to aid in determining if homology exists. Provisional nomenclature is suggested for use in the interim until homology can be established.
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Genotypes of milk protein genes, alpha S1 -casein ( CSN1S1), beta-casein ( CSN2), kappa-casein ( CSN3) and beta-lactoglobulin ( LGB), were detected in 440 individuals of Czech Fleckvieh breed using a PCR-RFLP method. Breeding values of genotyped animals were obtained from the Official Database of Progeny Testing. A granddaughter design including 5 grandsires, 33 sons and 402 granddaughters was used for evaluation. Statisti - cal analysis was carried out in SAS program using a restricted maximum likelihood method (REML). The aim of this study was to determine allele and genotype frequencies of observed genes and to find the relation between genotypes of genes and milk production parameters expressed by the breeding values of animals. The positive findings of frequencies of CSN3 allele B (0.38) and genotype BB (13%) were detected in the observed population.
The induction of Fos-like immunoreactivity (FLI) was used to determine the brain localization affected by b-casomorphin-7 (b-CM7). Peripheral administration of human b-CM7 at different doses (5, 10 and 30 mg/kg, IV for 1 hour) to rats induced moderate to strong FLI in discrete brain regions including the nucleus accumbens, caudate putamen, ventral tegmental and median raphe nucleus, and orbitofrontal, prefrontal, parietal, temporal, occipital and entorhinal cortex. All of the above areas have been shown to be altered either functionally or anatomically in patients with schizophrenia, and most have been shown to be functionally abnormal in autism. Some of these brain areas are originators or components of dopaminergic, serotoninergic and GABA-ergic pathways, suggesting that b-CM7 can affect the function of all of these systems. The role of some other affected areas in emotional and motivated behavior, social adaptation, hallucinations and delusions suggests that b-CM7, which was found in high concentration in the CSF, blood and urine of patients with either schizophrenia or autism, may be relevant to schizophrenia and autism. Induction of FLI in the above brain areas by a moderate dose (10 mg/kg) of b-CM7 was attenuated significantly, or blocked, by pretreatment with naloxone (2 mg/kg, IP). It is concluded that human b-CM7 can cross the blood-brain barrier, activate opioid receptors and affect brain regions similar to those affected by schizophrenia and autism.
In a previous study we showed that &bgr;-casomorphin-7 (&bgr;-CM7) is taken up by brain regions relevant to schizophrenia and autism. The present experiment was designed to find whether &bgr;-CM7 has any behavioral or analgesic effects in rats. About 65 seconds after treatment with different doses of &bgr;-CM7, rats became restless and ran violently, with teeth chattering and with rapid respiration. Seven minutes later, the rats became inactive with less walking, distancing themselves from the other rat in the same cage, and sitting in, or putting their head against, the corner of the cage. The sound response was reduced and social interaction was absent. One hour later, the rats showed hyperdefensiveness. The above behavioral effects of &bgr;-CM7 did not occur when rats were pretreated with naloxone (2 mg/kg, IP). The rats receiving saline did not show any behavioral changes throughout the 2 hour period of observation. &bgr;-CM7 also demonstrated analgesic effects, which could be blocked by naloxone. The results suggest that &bgr;-CM7 may play a role in behavioral disorders such as autism and schizophrenia.