Inbreeding is the reproduction from the mating of two genetically related parents. Inbreeding results in increased homozygosity, which can increase the chances of offspring being affected by recessive or deleterious traits. This generally leads to a decreased fitness of a population, which is called inbreeding depression.

Livestock breeders often practice controlled breeding to eliminate undesirable characteristics within a population, which is also coupled with culling of what is considered unfit offspring, especially when trying to establish a new and desirable trait in the stock.

In plant breeding, inbred lines are used as stocks for the creation of hybrid lines to make use of the effects of heterosis. Inbreeding in plants also occurs naturally in the form of self-pollination.

Results[link]

Inbreeding may result in a far higher phenotypic expression of deleterious recessive genes within a population than would normally be expected.^[1] As a result, first-generation inbred individuals are more likely to show physical and health defects, including:

• Reduced fertility both in litter size and sperm viability
• Increased genetic disorders
• Fluctuating facial asymmetry
• Lower birth rate
• Higher infant mortality
• Slower growth rate
• Smaller adult size
• Loss of immune system function

Natural selection works to remove individuals with the above types of traits from the gene pool. Therefore, many more individuals in the first generation of inbreeding will never live to reproduce. Over time, with isolation such as a population bottleneck caused by purposeful (assortative) breeding or natural environmental stresses, the deleterious inherited traits are culled.

Island species are often very inbred, as their isolation from the larger group on a mainland allows for natural selection to work upon their population. This type of isolation may result in the formation of race or even speciation, as the inbreeding first removes many deleterious genes, and allows expression of genes that allow a population to adapt to an ecosystem. As the adaptation becomes more pronounced the new species or race radiates from its entrance into the new space, or dies out if it cannot adapt and, most importantly, reproduce.^[2]

The reduced genetic diversity that results from inbreeding may mean a species may not be able to adapt to changes in environmental conditions. Each individual will have similar immune systems, as immune systems are genetically based. Where a species becomes endangered, the population may fall below a minimum whereby the forced interbreeding between the remaining animals will result in extinction.

Natural breedings include inbreeding by necessity, and most animals only migrate when necessary. In many cases, the closest available mate is a mother, sister, grandmother, father, grandfather... In all cases the environment presents stresses to remove those individuals who cannot survive because of illness from the population.

There was an assumption that wild populations do not inbreed; this is not what is observed in some cases in the wild. However, in species such as horses, animals in wild or feral conditions often drive off the young of both genders, thought to be a mechanism by which the species instinctively avoids some of the genetic consequences of inbreeding.^[3] In general, many mammal species including humanity's closest primate relatives avoid close inbreeding possibly due to the deleterious effects.^[4]

Examples[link]

The cheetah was once reduced by disease, habitat restriction, overhunting of prey, and competition from other predators to a very small number of individuals.^[5][6] All cheetahs now come from this very small gene pool. Should a virus appear that none of the cheetahs have resistance to, extinction is always a possibility. Currently, the threatening virus is feline infectious peritonitis, which has a disease rate in domestic cats from 1%–5%; in the cheetah population it is ranging between 50% to 60%. The cheetah is also known, in spite of its small gene pool, for few genetic illnesses.

In the South American sea lion, there was concern that recent population crashes would reduce genetic diversity. Historical analysis indicated that a population expansion from just two matrilineal lines were responsible for most individuals within the population. Even so, the diversity within the lines allowed for great variation in the gene pool that may help to protect the South American sea lion from extinction.^[7]

In lions, prides are often followed by related males in bachelor groups. When the dominant male is killed or driven off by one of these bachelors, a father may be replaced with his son. There is no mechanism for preventing inbreeding or to ensure outcrossing. In the prides, most lionesses are related to one another. If there is more than one dominant male, the group of alpha males are usually related. Two lines are then being "line bred". Also, in some populations such as the Crater lions, it is known that a population bottleneck has occurred. Researchers found far greater genetic heterozygosity than expected.^[8] In fact, predators are known for low genetic variance, along with most of the top portion of the tropic levels of an ecosystem.^[9] Additionally, the alpha males of two neighboring prides can potentially be from the same litter; one brother may come to acquire leadership over another's pride, and subsequently mate with his 'nieces' or cousins. However, killing another male's cubs, upon the takeover, allows for the new selected gene complement of the incoming alpha male to prevail over the previous male. There are genetic assays being scheduled for lions to determine their genetic diversity. The preliminary studies show results inconsistent with the outcrossing paradigm based on individual environments of the studied groups.^[8]

Calculation[link]

The inbreeding is computed as a percentage of chances for two alleles to be identical by descent. This percentage is called "inbreeding coefficient". There are several methods to compute this percentage, the two main ways are the path method^[10] and the tabular method.^{[11][unreliable source?]}

Typical inbreeding coefficient percentages are as follows, assuming no previous inbreeding between any parents:

• Father/daughter, mother/son or brother/sister → 25% (¹⁄₄)
• Grandfather/granddaughter or grandmother/grandson → 12.5% (¹⁄₈)
• Half-brother/half-sister → 12.5% (¹⁄₈)
• Uncle/niece or aunt/nephew → 12.5% (¹⁄₈)
• Great-grandfather/great-granddaughter or great-grandmother/great-grandson → 6.25% (¹⁄₁₆)
• Half-uncle/niece or half-aunt/nephew → 6.25% (¹⁄₁₆)
• First cousins → 6.25% (¹⁄₁₆)
• First cousins once removed or half-first cousins → 3.125% (¹⁄₃₂)
• Second cousins or first cousins twice removed → 1.5625% (¹⁄₆₄)
• Second cousins once removed or half-second cousins → 0.78125% (¹⁄₁₂₈)
• Third cousins or second cousins twice removed → 0.390625% (¹⁄₂₅₆)
• Third cousins once removed or half-third cousins → 0.1953125% (¹⁄₅₁₂)

An inbreeding calculation may be used to determine the general genetic distance among relatives by multiplying by two, because any progeny would have a 1 in 2 risk of actually inheriting the identical alleles from both parents.

For instance, the parent/child or sibling/sibling relationships have 50% identical genetics.

Domestic animals[link]

An intensive form of inbreeding where an individual S is mated to his daughter D1, granddaughter D2 and so on, in order to maximise the percentage of S's genes in the offspring. D3 would have 87.5% of his genes, while D4 would have 93.75%.^[12]

Breeding in domestic animals is assortative breeding primarily (see selective breeding). Without the sorting of individuals by trait, a breed could not be established, nor could poor genetic material be removed. Homozygosity is the case where similar or identical alleles combine to express a trait that is not otherwise expressed (recessiveness). Inbreeding, through homozygosity, exposes recessive alleles. Inbreeding is used to reveal deleterious recessive alleles, which can then be eliminated through assortative breeding or through culling.

Inbreeding is used by breeders of domestic animals to fix desirable genetic traits within a population or to attempt to remove deleterious traits by allowing them to manifest phenotypically from the genotypes. Inbreeding is defined as the use of close relations for breeding such as mother to son, father to daughter, brother to sister.

Breeders must cull unfit breeding suppressed individuals and/or individuals who demonstrate either homozygosity or heterozygosity for genetic based diseases.^[13] The issue of casual breeders who inbreed irresponsibly is discussed in the following quotation on cattle:

Meanwhile, milk production per cow per lactation increased from 17,444 lbs to 25,013 lbs from 1978 to 1998 for the Holstein breed. Mean breeding values for milk of Holstein cows increased by 4,829 lbs during this period.^[14] High producing cows are increasingly difficult to breed and are subject to higher health costs than cows of lower genetic merit for production (Cassell, 2001). Intensive selection for higher yield has increased relationships among animals within breed and increased the rate of casual inbreeding. Many of the traits that affect profitability in crosses of modern dairy breeds have not been studied in designed experiments. Indeed, all crossbreeding research involving North American breeds and strains is very dated (McAllister, 2001) if it exists at all.^[15]

Linebreeding is a form of inbreeding. There is no clear distinction between the two terms, but linebreeding may encompass crosses between individuals and their descendants or two cousins.^[12][16] This method can be used to increase a particular animal's contribution to the population.^[12] While linebreeding is less likely to cause problems in the first generation than does inbreeding, over time, linebreeding can reduce the genetic diversity of a population and cause problems related to a too-small genepool that may include an increased prevalence of genetic disorders and inbreeding depression.^{[citation needed]}

Outcrossing is where two unrelated individuals have been crossed to produce progeny. In outcrossing, unless there is verifiable genetic information, one may find that all individuals are distantly related to an ancient progenitor. If the trait carries throughout a population, all individuals can have this trait. This is called the founder's effect. In the well established breeds, that are commonly bred, a large gene pool is present. For example, in 2004, over 18,000 Persian cats were registered.^[17] A possibility exists for a complete outcross, if no barriers exist between the individuals to breed. However it is not always the case, and a form of distant linebreeding occurs. Again it is up to the assortative breeder to know what sort of traits both positive and negative exist within the diversity of one breeding. This diversity of genetic expression, within even close relatives, increases the variability and diversity of viable stock.^[18]

The two dog sites above also point out that in the registered dog population, the onset of large numbers of casual breeders has corresponded with an increase in the number of genetic illnesses of dogs by not understanding how, why and which traits are inherited. The dog sites indicate that the largest percentage of dog breeders in the US are casual breeders. Therefore the investment in a papered animal,with an expected short term profit, motivates some to ignore the practice of culling. Casual breeders in companion animals often ignore breeding restrictions within their contracts with source companion animal breeders. The casual breeders breed the very culls that a genetics based breeder has released as a pet. The casual breeder was also cited in the quotes above on cattle raising.

Laboratory animals[link]

Systematic inbreeding and maintenance of inbred strains of laboratory mice and rats is of great importance for biomedical research. The inbreeding guarantees a consistent and uniform animal model for experimental purposes and enables genetic studies in congenic and knock-out animals. The use of inbred strains is also important for genetic studies in animal models, for example to distinguish genetic from environmental effects.

Humans[link]

Genetic disorders[link]

Autosomal recessive disorders occur in individuals who have two copies of the gene for a particular recessive genetic mutation. Except in certain rare circumstances, such as new mutations or uniparental disomy, both parents of an individual with such a disorder will be carriers of the gene. These carriers do not display any signs of the mutation and may be unaware that they carry the mutated gene. Since relatives share a higher proportion of their genes than do unrelated people, it is more likely that related parents will both be carriers of the same recessive gene, and therefore their children are at a higher risk of a genetic disorder. The extent to which the risk increases depends on the degree of genetic relationship between the parents: The risk is greatest when the parents are close relatives and lower for relationships between more distant relatives, such as second cousins, though still greater than for the general population.^[19]

A 1998 review found 1-4% increased morbidity for offsprings of first cousin marriages compared to offsprings of unrelated parents. A 1994 review found 4.4% increased mortality for offspring of first cousins. After controlling for several sociodemographic factors, infant mortality for offspring of first cousins had odds ratios of 1.36, 1.28, and 1.32 for the neonatal, postneonatal, and infant period. There has been little research on how inbreeding affects common adult disorder although some preliminary evidence support effects on many such disorders including cardiovascular diseases and common cancers. Many previously not identified genetic disorders have first been recognized in highly endogamous communities and the mutation causing the disease may be unique to such communities.^[20] A review of 48 studies of children born to cousins found that most of the children were healthy, with birth defects affecting 4% of births for consanguineous couples compared to 2% for the general population.^[21]

Children of parent-child or sibling-sibling unions are at increased risk compared to cousin-cousin unions. Studies suggest that 20-36% of these children will die or have major disability due to the inbreeding.^[22]

Royalty and nobility[link]

Royal intermarriage was often practised to protect property, wealth and position.

• In ancient Egypt, royal women carried the bloodlines and so it was advantageous for a pharaoh to marry his sister or half-sister;^[23] in such cases a special combination between endogamy and polygamy is found. Normally the old ruler's eldest son and daughter (who could be either siblings or half-siblings) became the new rulers. All rulers of the Ptolemaic dynasty from Ptolemy II were married to their brothers and sisters, so as to keep the Ptolemaic blood "pure" and to strengthen the line of succession. Cleopatra VII (also called Cleopatra VI) and Ptolemy XIII, who married and became co-rulers of ancient Egypt following their father's death, are the most widely known example.^[24]
• Among European monarchies Jean V of Armagnac formed a rare brother-sister relationship. Also other royal houses, such as the Wittelsbachs had marriages among aunts, uncles, nieces and nephews. The British royal family had several marriages as close as the first cousin, but none closer.
• One of the most famous example of a genetic disorder aggravated by royal family intermarriage was the House of Habsburg, which inmarried particularly often. Famous in this case is the Habsburger (Unter) Lippe (Habsburg jaw/Habsburg lip/"Austrian lip") (mandibular prognathism), typical for many Habsburg relatives over a period of six centuries.^[25] The condition progressed through the generations to the point that the last of the Spanish Habsburgs, Charles II of Spain, could not properly chew his food.^[26]
• Besides the jaw deformity, Charles II also had a huge number of other genetic physical, intellectual, sexual, and emotional problems. It is speculated that the simultaneous occurrence in Charles II of two different genetic disorders: combined pituitary hormone deficiency and distal renal tubular acidosis could explain most of the complex clinical profile of this king, including his impotence/infertility which in the last instance led to the extinction of the dynasty.^[27]
• Another famous genetic disease that circulated among European royalty was hemophilia. Because the progenitor, Queen Victoria, was in a first cousin marriage, it is often mistakenly believed that the cause was consanguinity. However, this disease is generally not aggravated by cousin marriages, although rare cases of hemophilia in girls (though not including Victoria) are thought to result from the union of hemophiliac men and their cousins.^[28][29]
• Intermarriage within European royal families has declined in relation to the past. Inter-nobility marriage was used as a method of forming political alliances among elite power-brokers. These ties were often sealed only upon the birth of progeny within the arranged marriage. Thus marriage was seen as a union of lines of nobility, not of a contract between individuals as it is seen today.
• Some Peruvian Sapa Incas married their sisters; in such cases a special combination between endogamy and polygamy is found. Normally the son of the old ruler and the ruler's oldest (half-)sister became the new ruler. The Inca had an unwritten rule that the new ruler must be a son of the Inca and his wife and sister. He then had to marry his sister (not half-sister), which ultimately led to the catastrophic Huáscar's reign, culminating in a civil war and then fall of the empire.
• The Chakri Dynasty of Thailand has included marriages between cousins as well as more close relatives. The current king, Bhumibol Adulyadej is a first-cousin once removed of his wife, Sirikit, the two being respectively a grandson and a great-granddaughter of Chulalongkorn. The parents of the king's father, Mahidol Adulyadej, were half-siblings, both being children of Mongkut by different mothers.
• Queen Elizabeth II and her husband Prince Philip, Duke of Edinburgh are third cousins as a result of them both being directly descended from Queen Victoria; as well as second cousins once removed as a result of being directly descended from Christian IX of Denmark.^[30]

Some inbreeding may enhance fertility rate[link]

A recent study in Iceland by the deCODE genetics company, published by the journal Science, found that third cousins produced more children and grandchildren, suggesting that "in spite of the fact that bringing together two alleles of a recessive trait may be bad, there is clearly some biological wisdom in the union of relatively closely related people".^[31] For hundreds of years, inbreeding was historically unavoidable in Iceland due to its then tiny and isolated population.^[32]

See also[link]

• Genetic diversity
• Coefficient of relationship
• Consanguinity
• Cousin marriage
• Exogamy
• F-statistics
• Genetic sexual attraction
• Heterozygote advantage
• Identical ancestors point
• Inbreeding depression
• Incest
• Insular dwarfism
• Intellectual inbreeding
• Linebreeding
• List of coupled cousins
• Outbreeding depression
• Outcrossing
• Prohibited degree of kinship
• Selective breeding
• Self-incompatibility in plants (how some plants avoid inbreeding)

References[link]

External links[link]

• Dale Vogt, Helen A. Swartz and John Massey, 1993. Inbreeding: Its Meaning, Uses and Effects on Farm Animals. University of Missouri, Extension.
• Consanguineous marriages with global map

Harold & Kumar is the common name for a series of stoner comedy films starring John Cho (Harold) and Kal Penn (Kumar). The first film, Harold & Kumar Go to White Castle, was released on July 30, 2004 by New Line Cinema and spawned a sequel titled Harold & Kumar Escape from Guantanamo Bay, released four years later. A Very Harold & Kumar 3D Christmas, the third installment of the series, opened nationwide in the U.S. on 4 November 2011.

The film series has become a critical and financial success. The first two films, produced on a total budget of US$21 million, grossed $73 million worldwide. In addition to their box office grosses, the first two films were extremely successful on home video. The series has been released on both Blu-ray and DVD.

Series[link]

[edit] Harold & Kumar Go to White Castle (2004)

Harold Lee and Kumar Patel are two Asian-American (Korean and Indian) stoners who get the munchies and embark on a quest throughout New Jersey for White Castle burgers after seeing them advertised on TV. On their way they encounter many obstacles, including a gang of extreme sports punks, a raccoon with an attitude, a group of Asian nerds, a racist police department, a cheetah that has escaped from a zoo, and an out-of-control Neil Patrick Harris.

[edit] Harold & Kumar Escape from Guantanamo Bay (2008)

Following the events of Harold & Kumar Go to White Castle, Harold Lee and Kumar Patel fly to Amsterdam so Harold can pursue a budding romance with his vacationing neighbor. After arrival at the airport, Kumar creates trouble while going through security in order to get weed on the plane. The pair run into Vanessa, Kumar's ex-girlfriend, and her fiancé Colton, another old college buddy who helped Harold with getting a job at Brewster-Keagan, at the airport. Harold and Kumar board the plane, and mid-flight, an elderly woman sees Kumar lighting a smokeless bong. She thinks that it is a bomb, and screams "Terrorist!", causing the passengers to be alerted when Kumar is holding the bong. After a confusion of the words "bong" and "bomb", two undercover air marshals tackle Kumar; he drops the bong on the floor, which breaks and emits a pleasant-smelling, though visible, gas, causing another passenger to scream "Poison gas!". Air marshals tackle them and order the plane to return to the United States where Ron Fox, a neurotic Deputy Secretary of Homeland Security, in Washington, D.C. sends them to the Guantanamo Bay detention camp. Just as they are "forced to suck Big Bob's fat dick" or perform fellatio, they escape and enter the United States through Miami, Florida with the help of some Cuban refugees. They go to see a friend of theirs, Raza, who is hosting a bottomless party and he encourages them to travel to Texas in search of Colton, with hopes that he will be able to help them through his father, who is connected with several high political officials.

[edit] A Very Harold & Kumar 3D Christmas (2011)

In April 2009, Kal Penn accepted the position of Associate Director of the White House Office of Public Liaison in the Obama administration; when asked if his new job would mean no more Harold and Kumar films, he said, "That's probably true for now." ^[1]

A new film entitled A Very Harold & Kumar Christmas was announced on May 7, 2009, for release on December 5, 2010 at the earliest and possibly deferred to the 2011 holiday season.^[2] Jon Hurwitz and Hayden Schlossberg returned to write the film while Todd Strauss-Schulson directed. Greg Shapiro returned as producer with Kal Penn and John Cho reprising their title roles.^[3][4] Penn left his job with the White House on June 1, 2010 to reprise his role as Kumar in the third Harold & Kumar installment.^[5] After filming was completed, Penn returned to the White House. ^[6]

David Krumholtz, answering the last question of a Live Q&A Chat on TV.com that took place on March 12, 2010, mentioned that he and Eddie Kaye Thomas would probably be in the third Harold & Kumar film.

I do believe we will be in H&K3

—David Krumholtz, "Live Q&A Chat with David Krumholtz from CBS's Numb3rs! - TV.com". http://www.tv.com/live-qa-chat-with-david-krumholtz-from-cbs-numb3rs/story/21306.html. 

Neil Patrick Harris also returned for the film (which he confirmed on The Late Late Show with Craig Ferguson). He went as far as saying that he finished filming and that the film would be released in 3D (filmed with 3D cameras). Patton Oswalt has been confirmed to also star in the film.^[7] Amir Blumenfeld, of CollegeHumor fame, also appeared in the film.

Characters[link]

Harold Lee[link]

Harold Lee is a Korean American investment banker residing in New Jersey. The character was created by Jon Hurwitz and Hayden Schlossberg, and is portrayed by John Cho in all three films.

In Harold & Kumar Go to White Castle, Harold is a hard-working stoner from the northern part of New Jersey. Harold's lazy best friend and roommate, free spirit Kumar Patel, is not afraid to let go of his inhibitions, making Harold the symbolic personification of the suppressed Asian-American employee and student in the United States. Harold, at times, lets go of his inhibitions, but only during moments of extreme duress, to the point where he amazes even the free-spirited Kumar. Harold is the yin to Kumar's yang, with the both of them being united through their enjoyment of cannabis smoking after a long day's work and or leisurely fun (such as aboard an airplane in the sequel, and an after work "Friday night special" in the first film).

Harold's romantic life centers around John Hughes-like fancies (as is evidenced by his infatuation with film classics such as Sixteen Candles). Harold thinks that he'll wind up with a similarly repressed Korean-American young woman—Cindy Kim—who isn't as repressed as he thinks. The true object of Harold's desire, however, is Maria Perez (played by Paula Garces), who lives down the hall from him in his building.

In Harold & Kumar Escape from Guantanamo Bay, when embarking on their trip to Amsterdam they are arrested on the flight there because of Kumar testing out his "smokeless bong" in the airplane lavatory, followed up by being sent to Guantanamo Bay—only to be followed by another series of comedic events. In one of the flashbacks Kumar has, it is revealed that Harold used to be an emo kid back in college.

Kumar Patel[link]

Kumar Patel is an Indian American student residing in New Jersey. His family includes his father and brother, Saikat Patel. The character was created by Jon Hurwitz and Hayden Schlossberg, and is portrayed by Kal Penn in all three films.

In Harold & Kumar Go to White Castle, Kumar Patel is a 22-year-old college graduate. He shares an apartment with best friend, Harold Lee. Unlike Harold, Kumar is a free spirited and outgoing rebel, not afraid to do what he wants. Kumar is the yang to Harold's yin, with the both of them being united through their enjoyment of cannabis smoking after a long day's work and or leisurely fun (such as aboard an airplane in the sequel, and an after work "Friday night special" in the first film). Both his father and brother are successful doctors, and expect him to follow in their footsteps. Though not interested in school, Kumar is remarkably intelligent and knows how to perform complex surgical procedures, as shown in the film while looking for medicinal marijuana at the hospital.

In Harold & Kumar Escape from Guantanamo Bay, it is revealed that he had a girlfriend Vanessa in college, who introduced him to marijuana and transformed him from an uptight geek into the laid-back stoner he is today. She is about to get married to sleazy, deceptive frat boy Colton Graham (who disapproves of her marijuana habit), but Kumar interrupts the wedding and wins her back by reciting "Square Root of 3," a math themed love poem that he was afraid to show her in college. Harold, Kumar and Vanessa then go to Amsterdam to find Harold's love interest, Maria.

Neil Patrick Harris[link]

All three films feature Neil Patrick Harris playing a fictionalized version of himself. In the films, Harris is portrayed as a heavy drug user and womanizer, despite being openly gay in real life. In the third film, the fictional version of Harris is revealed to be pretending to be gay to draw attention away from his womanizing and appeared with his real-life partner David Burtka.

In an interview with Ain't It Cool News, Neil Patrick Harris revealed that the series' writers were discussing the possibility of a spin-off movie based on his fictional persona. ^[8]

Rosenberg and Goldstein[link]

Rosenberg and Goldstein are two Jewish friends and counterparts of Harold and Kumar portrayed by Eddie Kaye Thomas and David Krumholtz. They live in the same apartment building as Harold and Kumar. In the third movie, Goldstein stated he had converted to Christianity after marrying his wife.

There has been discussion of them getting their own spin-off movie, which would follow the characters during the events of the original film (theoretically titled Rosenberg & Goldstein Go to Hot Dog Heaven).^[9] The duo is based on the characters Rosencrantz and Guildenstern from the Shakespeare play, Hamlet.

Reception[link]

Box-office performance[link]

Critical reception[link]

References[link]

External links[link]

• Official website
• Harold & Kumar Go to White Castle at the Internet Movie Database
• Harold & Kumar Escape from Guantanamo Bay at the Internet Movie Database
• A Very Harold & Kumar Christmas at the Internet Movie Database