A major problem that bison face today is a lack of genetic diversity due to the population bottleneck the species experienced during its near-extinction event.
Another genetic issue is the entry of genes from domestic cattle into the bison population, through hybridization.

Officially, the "American buffalo" is classified by the United States government as a type of cattle, and the government allows private herds to be managed as such.
This is a reflection of the characteristics that bison share with cattle.
 Though the American bison is not only a separate species, but also is usually regarded as being in a separate genus from domestic cattle (Bos taurus), they clearly have a lot of genetic compatibility and American bison can interbreed with cattle, although only the female offspring are fertile in the first generation.
These female hybrids can be bred back to either bison or domestic bulls, resulting in either 1/4 or 3/4 bison young.
Female offspring from this cross are also fertile, but males are not reliably fertile unless they are either ​⁷⁄₈ bison or ​⁷⁄₈ domestic.
Moreover, when they do interbreed, crossbreed animals in the first generation tend to look very much like purebred bison, so appearance is completely unreliable as a means of determining what is a purebred bison and what is a crossbred cow.
 Many ranchers have deliberately crossbred their cattle with bison, and some natural hybridization could be expected in areas where cattle and bison occur in the same range.
Since cattle and bison eat similar food and tolerate similar conditions, they have often been in the same range together in the past, and opportunity for crossbreeding may sometimes have been common.

In recent decades, tests were developed to determine the source of mitochondrial DNA in cattle and bison, and most private "buffalo" herds were actually crossbred with cattle, and even most state and federal buffalo herds had some cattle DNA.
With the advent of nuclear microsatellite DNA testing, the number of herds known to contain cattle genes has increased.
Though about 500,000 bison exist on private ranches and in public herds, perhaps only 15,000 to 25,000 of these bison are pure and not actually bison-cattle hybrids. "
DNA from domestic cattle (Bos taurus) has been detected in nearly all bison herds examined to date."
 Significant public bison herds that do not appear to have hybridized domestic cattle genes are the Yellowstone Park bison herd, the Henry Mountains bison herd, which was started with bison taken from Yellowstone Park, the Wind Cave bison herd, and the Wood Buffalo National Park bison herd and subsidiary herds started from it, in Canada.

A landmark study of bison genetics performed by James Derr of Texas A&M University corroborated this.
The Derr study was undertaken in an attempt to determine what genetic problems bison might face as they repopulate former areas, and it noted that bison seem to be adapting successfully, despite their apparent genetic bottleneck.
One possible explanation for this might be the small amount of domestic cattle genes that are now in most bison populations, though this is not the only possible explanation for bison success.

In the study, cattle genes were also found in small amounts throughout most national, state and private herds. "
The hybridization experiments conducted by some of the owners of the five foundation herds of the late 1800s, have left a legacy of a small amount of cattle genetics in many of our existing bison herds."
He also said, "All of the state owned bison herds tested (except for possibly one) contain animals with domestic cattle mtDNA."
 It appears that the one state herd that had no cattle genes was the Henry Mountains bison herd; the Henry Mountain herd was started initially with transplanted animals from Yellowstone Park.
However, the extension of this herd into the Book Cliffs of central Utah involved mixing the founders with additional bison from another source, so it is not known if the Book Cliffs extension of the herd is also free of cattle hybridization.

A separate study
A major problem that bison face today is a lack of genetic diversity due to the population bottleneck the species experienced during its near-extinction event. Another genetic issue is the entry of genes from domestic cattle into the bison population, through hybridization.
Officially, the "American buffalo" is classified by the United States government as a type of cattle, and the government allows private herds to be managed as such. This is a reflection of the characteristics that bison share with cattle.  Though the American bison is not only a separate species, but also is usually regarded as being in a separate genus from domestic cattle (Bos taurus), they clearly have a lot of genetic compatibility and American bison can interbreed with cattle, although only the female offspring are fertile in the first generation. These female hybrids can be bred back to either bison or domestic bulls, resulting in either 1/4 or 3/4 bison young. Female offspring from this cross are also fertile, but males are not reliably fertile unless they are either ​⁷⁄₈ bison or ​⁷⁄₈ domestic. Moreover, when they do interbreed, crossbreed animals in the first generation tend to look very much like purebred bison, so appearance is completely unreliable as a means of determining what is a purebred bison and what is a crossbred cow.  Many ranchers have deliberately crossbred their cattle with bison, and some natural hybridization could be expected in areas where cattle and bison occur in the same range. Since cattle and bison eat similar food and tolerate similar conditions, they have often been in the same range together in the past, and opportunity for crossbreeding may sometimes have been common.
In recent decades, tests were developed to determine the source of mitochondrial DNA in cattle and bison, and most private "buffalo" herds were actually crossbred with cattle, and even most state and federal buffalo herds had some cattle DNA. With the advent of nuclear microsatellite DNA testing, the number of herds known to contain cattle genes has increased. Though about 500,000 bison exist on private ranches and in public herds, perhaps only 15,000 to 25,000 of these bison are pure and not actually bison-cattle hybrids. "DNA from domestic cattle (Bos taurus) has been detected in nearly all bison herds examined to date."  Significant public bison herds that do not appear to have hybridized domestic cattle genes are the Yellowstone Park bison herd, the Henry Mountains bison herd, which was started with bison taken from Yellowstone Park, the Wind Cave bison herd, and the Wood Buffalo National Park bison herd and subsidiary herds started from it, in Canada.
A landmark study of bison genetics performed by James Derr of Texas A&M University corroborated this. The Derr study was undertaken in an attempt to determine what genetic problems bison might face as they repopulate former areas, and it noted that bison seem to be adapting successfully, despite their apparent genetic bottleneck. One possible explanation for this might be the small amount of domestic cattle genes that are now in most bison populations, though this is not the only possible explanation for bison success.
In the study, cattle genes were also found in small amounts throughout most national, state and private herds. "The hybridization experiments conducted by some of the owners of the five foundation herds of the late 1800s, have left a legacy of a small amount of cattle genetics in many of our existing bison herds." He also said, "All of the state owned bison herds tested (except for possibly one) contain animals with domestic cattle mtDNA."  It appears that the one state herd that had no cattle genes was the Henry Mountains bison herd; the Henry Mountain herd was started initially with transplanted animals from Yellowstone Park. However, the extension of this herd into the Book Cliffs of central Utah involved mixing the founders with additional bison from another source, so it is not known if the Book Cliffs extension of the herd is also free of cattle hybridization.
A separate study 
American bison