Title:  Method of selecting non-diabetogenic milk or milk products and milk or milk products so selected

United States Patent:  6,451,368

Issued:  September 17, 2002

Inventors:  Elliott; Robert B (Auckland, NZ); Hill; Jeremy P (Palmerston North, NZ)

Assignee:  New Zealand Dairy Board (Wellington, NZ); A2 Corporation Limited (Dunedin, NZ)

Appl. No.:  836778

Filed:  August 8, 1997

PCT Filed:  November 3, 1995

PCT NO:  PCT/NZ95/00114

371 Date:  August 8, 1997

102(e) Date:  August 8, 1997

PCT PUB.NO.:   WO96/14577

PCT PUB. Date:  May 17, 1996

The invention is based on the discovery that certain variants of .beta.-casein may induce Type-1 diabetes in susceptible individuals while other variants do not. The invention consists of the selection of non-diabetogenic milk producing cows and recovering and processing their milk and milk products. Another aspect of the invention is selectively breeding cows which produce the non-diabetogenic milk.

DISCLOSURE OF THE INVENTION

Accordingly, the invention may be said broadly to consist in a method of selecting milk for feeding to diabetes susceptible individuals which comprises testing milk from identified cows for the presence of variants of .beta.-casein and selecting those cows whose milk contains any non-diabetogenic variant and does not contain any diabetogenic variant, and milking separately the non-diabetogenic variant milk producing cows and recovering and maintaining their milk separately from milk from any other source.

Preferably said non-diabetogenic variant is the A2 variant of .beta.-casein.

Alternatively said non-diabetogenic variant is the A3, D or E variant of .beta.-casein.

Preferably said diabetogenic variant is the A1 variant of .beta.-casein.

Alternatively, said diabetogenic variant is any one of the B, C and F variants.

Preferably, said recovered milk is tested for the presence of any diabetogenic variant and discarded if any is found.

Alternatively, said method of testing comprises the use of mass spectrometry.

In one embodiment said mass spectrometry comprises electro spray ionisation mass spectrometry.

Alternatively, said mass spectrometry comprises fast-atomic bombardment mass spectrometry.

Preferably, said method of testing comprises polyacrylamide gel electrophoresis using an acid urea gel.

Preferably, said process includes the additional step of processing said milk into milk products.

There are a large number of processes known to those skilled in the art for converting milk into milk products. These range from separating cream from whole milk to produce skim milk through to the use of microfiltration and ultrafiltration to produce a wide range of products such as those described in international application PCT/NZ95/00086, the specification, claims and drawings of which are incorporated herewith by reference.

One particular product of interest from the aforementioned international application is milk protein concentrate. This may be prepared by other processes such as that described in IDF Special Issue No. 9201, (1991), Chapter 5 entitled "Milk Protein Concentrate", A. Novak.

Another milk product according to the invention is casein derived from non-diabetogenic milk by any well known casein producing process such as described in Southward et al, 1980.

The invention may be said broadly to consist in milk selected according to the process herein above defined.

The invention may also be said broadly to consist in a non-diabetogenic milk product prepared by any one of the processes described herein above.

The invention may also be said broadly to consist in a method for reducing the risk of contracting type 1 diabetes in a susceptible individual which comprises restricting the milk or milk product intake of that individual to milk containing only a non-diabetic variant of beta casein.

Preferably, said susceptible individual is an infant or young child.

The invention may also be said broadly to consist in a method of selecting milk for feeding to a Type-l diabetes susceptible individual which comprises testing milk from identified cows for the presence of the hexapeptide Pro-Gly-Pro-Ile-His-Asn (SEQ ID NO: 1), or a protein fragment containing the hexapeptide Pro-Gly-Pro-Ile-His-Asn (SEQ ID NO: 1) and selecting those cows whose milk does not contain said hexapeptide or said protein fragment containing said hexapeptide, and milking separately the cows whose milk does not contain the said hexapeptide or said protein fragment containing said hexapeptide and maintaining their milks separately from milk from any other source.

Preferably, said separated milk is also tested for the presence of said hexapeptide or said protein fragment containing said hexapeptide and any milk which does contain said hexapeptide or said protein containing hexapeptide is discarded.

Preferably, the method of testing for said hexapeptide is by using chromatographic purification of said hexapeptide followed by amino acid sequencing.

Preferably, said process includes the additional step of processing said milk into milk products.

The invention may be said broadly to consist in milk selected according to the process herein above defined.

The invention may also be said broadly to consist in a non-diabetogenic milk product prepared by any one of the processes described herein above.

Preferably, said susceptible individual is an infant or young child.

In another embodiment the invention may be said broadly to consist in a method for selecting breeding cows which produce daughters whose milk is not diabetogenic to susceptible children which comprises determining the genotype of said cows and selecting those whose daughters produce milk which does not contain the diabetogenic factor present in .beta.-casein.

Alternatively, the invention may be said broadly to consist in a process for selectively breeding bulls which produce daughters whose milk does not contain the diabetogenic factor present in .beta.-casein which comprises determining the genotype of said bulls and selecting those which daughters which produce milk which does not contain the diabetogenic factor present in .beta.-casein.

Preferably, the phenotyping of daughters to determine the genotype of said bull is done by testing the milk of said daughters for absence of diabetogenic variants of .beta.-casein and the presence of non-diabetogenic variants of .beta.-casein.

Alternatively, said cows or bulls are genotyped directly by using appropriate probes and polymerase chain reaction technology.

In another embodiment the invention may be said broadly to consist in cows selected in accordance with the immediately preceding method.

In a still further embodiment the invention may be said broadly to consist in bulls selected in accordance with the above defined method.

In a still further embodiment the invention may be said broadly to consist in semen of bulls selected in accordance with the above defined method.

In an alternative to any of the above processes or products the milk or milk product is goat's milk or milk product, sheep's milk or milk product, buffalo's milk or milk product, or milk or milk product from any other mammal which is fit for human consumption.

Claim 1 of 22 Claims

We claim:

1. A method of producing milk for administration to a diabetes susceptible individual, comprising selecting a lactating bovine cow whose milk contains non-diabetogenic variants of .beta.-casein, which have a proline at amino acid position 67, and does not contain diabetogenic variants of .beta.-casein, which have a histidine at amino acid position 67, milking the so selected bovine cow, and recovering the milk so produced.
 

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