1. Learning outcomes: At the end of the module the reader will know
Inbreeding
Consanguinity
Inbreeding co-efficient
Inbreeding depression
Classical examples of Inbreeding depression
Inbreeding coefficient and Inbreeding depression
Bi-parental reproduction has its own importance in natural selection and evolution. In which, a limited
number of mutations, which are not too injurious, to be carried by the species furnish an almost infinite
field of possible variation through which species may work its way under natural selection. But, at the
same time, in bi-parental reproduction, there may have breeding or mating between closely related
individuals for example: brother-sister mating and father-daughter mating. Such kind of mating
practices are called Inbreeding.
In another word, Inbreeding is a mating practice among organism of common ancestry; it is contrary to
out-breeding, which is the mating practice of unrelated individuals. The inbreeding has various pro and
cons. In genetics, it is an important practice, for retention of desirable characteristics or the elimination
of undesirable ones. For course of evolution, variation in gene pool is essential; in the same way for
perpetuation and existence of any species variation in gene pool should be maintained; and to maintain
variation in gene pool inbreeding should be avoided. But, at the same time; to maintain homogeneity in
offsprings inbreeding is essential. Sometimes, it is the only way to perpetuate any species or group of
organism in the circumstances of limited number of eligible mating population.
According to Jacquard (1975) Inbreeding’ is used to describe various related phenomena that all refer
to situations in which matings occur among relatives and to an increase in homozygosity associated
with such matings. However, they differ in the reference population that is used when calculating
inbreeding. Inbreeding is always a relative never an absolute measure. Therefore, inbreeding estimates
differ depending on the reference population to which they refer. It is this relativity that is responsible
for the different meanings of the term ‘inbreeding’, and for some of the misunderstanding that have
resulted. There is a historical precedence for such misunderstandings: Fisher (1965) never accepted
Wright’s inbreeding coefficients because they are relative (Keller and Waller, 2002). Three of the most
commonly used definitions of inbreeding are.
1.Pedigree inbreeding
An individual is considered inbred under this definition when the parents share ancestors. The extent of
inbreeding is related to the amount of ancestry that is shared by the parents of an inbred individual.
Pedigree information is used to determine the inbreeding coefficient. Although originally derived as a
correlation by Wright (1922).
2. Inbreeding as non-random mating
This refers to the degree of relatedness between mates relative to two mates chosen at random from the
population. An individual is considered inbred if its parents were more closely related than two
randomly chosen individuals. This type of inbreeding is relative to a random mating population of the
same size. Although it can be determined from pedigree data, this type of inbreeding is typically
measured by the deviation of the observed heterozygosity of an individual relative to the
heterozygosity expected under random mating
.
3. Inbreeding because of population sub division
When populations are subdivided into more or less isolated groups, inbreeding will also occur purely
because population size is restricted and genetic drift results. This occurs even if mating is random
within subpopulations (Crow and Kimura, 1970). This third definition of inbreeding corresponds to the
mean inbreeding coefficient expected in subpopulations under random mating.
Inbreeding is considered a problem in humans because inbreeding increases the chances of receiving a
deleterious recessive allele inherited from a common ancestor. Most studies are concerned with close
inbreeding, also known as incest, which usually sets a threshold at the level of first-cousin mating
(Thorn hill 1993).
Consanguinity
Two individuals are said to be consanguineous if they have at least one ancestor in common. In the
breeding of domestic animals consanguineous mating are frequently made. Occasionally matings are
made between very close relatives- father or sire and daughter, brother and sister etc. On the basis of
the theory of evolution, all individuals of a species are to some extent consanguineous, since all are
descended from a remote common ancestor. Consanguinity, and level of inbreeding, must therefore be
defined as applying only to relationships established after some evolutionary time point at which, for
convenience everyone is considered to be unrelated In practice, for human consanguinity common ancestors more remote than a great great grandfather are
rarely considered. In some human societies, more distant consanguinities may have social
significance, but from a genetic point of view the connection between two individuals who have one
great great great grandparent in common (fourth half cousins) is very vague (Cavalli-Sforza and
Bodmer 1971).
The progeny of consanguineous parents is, by definition, inbred. The inbred individuals may carry
double dose of a gene that was present in a single dose in common ancestor.
A recessive gene carried in a single dose in a common ancestor may remain hidden until it comes to
light for the first time in an inbred descendant. Therefore, recessive traits will occur with increased
frequency in the progeny of consanguineous mates.
The occurrence of consanguinity in a population depends on various factors viz. population structure,
migration, cultural practices and so on. Generally very close consanguineous mating are avoided in
human population. Practically, in all human societies incest is considered to be taboo. The degree of
relationship at which mating is considered incestuous may differ slightly from one society to another,
but, in general, parent-offspring and brother-sister mating are forbidden in all societies. Still,
incestuous union may be in most of the societies, but, they are negligible in proportion. Adam and
Neel (1967) have studied such children and most of them were the result of brother-sister mating and
father-daughter mating.
Marriage with a sib’s progeny (uncle-niece or aunt-nephew) is incestuous and not permissible in some
societies. In others, it is permissible with certain specific dispensation. Among many of Indian tribes
cross-cousin marriages are considered as preferential marriages.
By definition, an inbred individual is connected through both his father and his mother to the same
recent ancestor. He can thus receive two copies of a gene that was carried by common ancestor. Two
such copies are said to be identical, unless mutation has taken place in one of the line of descent,
which, however, is very rare event.
An individual who is homozygous for a given gene carries at a certain locus two homologous genes
that are physically identical but not necessarily identical by descent. This physical identity is what we
call identity by nature. Inbreeding makes an individual homozygous for genes that are identical by
descent.
Inbreeding co-efficient
Measurement of degree of inbreeding can be done by inbreeding co-efficient. The importance of
having a coefficient by means of which the extent of inbreeding can be expressed was brought out by
Pearl (1913). His coefficient was based on the smaller number of ancestors in each generation back of
an inbred individual, as compared with the maximum possible number. A separate coefficient is
obtained for each generation by the formula (Wright 1992).
Where is the ratio of actual to maximum possible ancestors in the n+1st generation. By
finding the ratio of a summation of these coefficients to a similar summation for the maximum possible
inbreeding in higher animals, viz., brother-sister mating, he obtains a single coefficient for the whole
pedigree.
This coefficient has the defect, as Pearl himself pointed out, that it may come out the same for systems
of breeding which we know are radically different as far as the effects of inbreeding are concerned.
In order to overcome this objection Pearl has devised a partial inbreeding index which is intended to
express the percentage of the inbreeding which is due to relationship between the father (sire) and
mother (dam), inbreeding being measured as above described. A coefficient of relationship is used in
this connection. There are two classes of effects which are ascribed to inbreeding: First, a decline in all
elements of vigour, as weight, fertility, vitality, etc., and second, an increase in uniformity within the
inbred offsprings, correlated with which is an increase in prepotency in outside crosses. Both of these
kinds of effects have ample experimental support as average (not necessarily unavoidable)
consequences of inbreeding. The best explanation of the decrease in vigour is dependent on the view
that Mendelian factors unfavorable to vigour in any respect are more frequently recessive than
dominant, a situation which is the logical consequence of the two propositions that mutations are more
likely to injure than improve the complex adjustments within an organism and that injurious dominant
mutations will be relatively promptly weeded out, leaving the recessive ones to accumulate, especially,
if they happen to be linked with favourable dominant factors. On this view, it may readily be shown
that the decrease in vigour on starting inbreeding in a previously random-bred population should be
directly proportional to the increase in the percentage of homozygosis. Numerous experiments with
plants and lower animals are in harmony with this view. Extensive experiments with guinea-pigs
conducted by the Bureau of Animal Industry are in close quantitative agreement. As for the other
effects of inbreeding, fixation of characters and increased prepotency, these are of course in direct
proportion to the percentage of homozygosis. Thus, if the percentage of homozygosis can be calculated
which would follow on the average from a given system of mating, a most natural coefficient of
inbreeding can be formed. The Wright (1992) has pointed out a method of calculating this percentage
of homozygosis which is applicable to the irregular systems of mating found in actual pedigrees as well
as to regular systems, which is widely different from Pearl’s coefficient, in many cases even as regards
the relative degree of inbreeding of two animals.
Taking the typical case, in which, there are an equal number of dominant and recessive genes (A and a)
in the population, the random-bred population will be composed of 25 per cent AA, 50 per cent Aa
and 25 per cent aa. Close inbreeding will tend to convert the proportions to 50 per cent AA, 50 per cent
aa, a change from 50 per cent homozygosis, to 100 per cent, homozygosis. For a natural coefficient of
inbreeding, a scale is needed which runs from 0 to 1, while the percentage of homozygosis is running
from, 50 per cent, to 100 per cent. The formula 2h-1, where h is the proportion of complete
homozygosis, gives the required value. This can also be written 1-2p where p is the proportion of
heterozygosis. It was already shown that the coefficient of correlation between uniting egg and sperm
is expressed by the same formula, f= 1-2p. In this way, the coefficient of inbreeding fb for a given
individual B, can be obtained by the use of the methods outlined.
The symbol rbc, for the coefficient of the correlation between B and C, may be used as a coefficient of
relationship. It has the value 0 in the case of two random individuals, 0.50 for brothers in a random
population and approaches 1.00 for individuals belonging to a closely inbred subline of the general
population.
In the general case in which dominants and recessives are not equally numerous, the composition of
the random-bred population is of the form x
2
AA , 2xy Aa, y2
aa. The percentage of homozygosis is
greater than 50 per cent. The rate of increase, however, under a given system of mating, is always
exactly proportional to that in the case of equality. The coefficient is thus of general application.
If an individual is inbred, his father and mother are connected in the pedigree by lines of descent from
a common ancestor or ancestors. The coefficient of inbreeding is obtained by a summation of
coefficients for every line by which the parents are connected, each line tracing back from the father to
a common ancestor and thence forward to the mother, and passing through no individual more than
once. The same ancestor may of course be involved in more than one line.
The path coefficient, for the path, father or sire (S) to offspring (O), is given by the formula
, where fs and fo are the coefficients of inbreeding for sire (father) and
offspring, respectively. The coefficient for the path, mother or dam to offspring, is similar.
In the case of grandfather or sire’s sire (G) and individual, It can be
, and for any ancestor (A) the coefficient pertaining to a given
line of descent where n is the number of generations between them in
this line.
The correlation between two individuals (rbc ) is obtained by a summation of the coefficients for all
connecting paths.
Alternative Methods of calculating the coefficient of inbreeding
An alternative method of computing F was proposed by Falconer (1989). In this technique the ‘Co
ancestries’ are used instead of working from the present back to common ancestors we work forward,
keeping a running tally, generation by generation, and compute the inbreeding that will result from the
mating now being made. This method is easier than path coefficients where the paths are often
numerous and complex but unnecessary for normal human pedigrees.
For regular systems of inbreeding, as used in the ‘inbred-hybrid’ system for breeding of animals it is
easy method for calculating F. In a a regular system of inbreeding, there is a certain type of mating
such as brother-sister, is repeated indefinitely. A recurrence equation calculates the F value of the
present generation from those of recent previous ones. e.g. the recurrence equation for repeated full sib
mating is:
Ft = 0.25 (1 + 2 F(t-1) + F (t-2))
Where is the Ft coefficient of the present generation, F(t-1) is the coefficient of the previous generation
and F(t-2)is the coefficient of the generation before that. It is important to note that recurrence equations
can only be used for regular systems of inbreeding. e.g. Three generations of full sib mating:-
First generation – F1 = 0.25 (1 + 0 + 0) = 0.25
Second generation – F2 = 0.25 (1 + 0.5 + 0) = 0.375
Third generation – F3 = 0.25 (1 + 0.75 + 0.25) = 0.5
For further elucidation, the value of F is shown in the following table as per different consanguineous
mating.
Table: values of F for consanguineous mating one generation, no previous inbreeding)
Self fertilization = 1/2
Full sibs, Parent-child, Double first cousins (first degree) = 1/4
Half sibs, Grandparent-grandchild, Uncle-niece, Double first cousins= 1/8
First cousins = 1/16
First cousins (once removed) = 1/32
Second cousins = 1/64
Second cousins (once removed) = 1/128
Third cousins = 1/256
Inbreeding Depression
Biologically, inbreeding has many harmful effects on the offspring. They may be homozygous for
certain lethal genes. In this way, reduced biological fitness in a given population as a result of
inbreeding is known as Inbreeding depression. Many studies have demonstrated reduced survival and
fecundity of inbred young (Wright 1977; Ralls and Ballou 1983, Sausman 1984, Templton and Read
1984). Biological fitness refers to ability to survive and reproduce. Inbreeding depression is often the
result of a population bottleneck.
A population bottleneck is a sharp reduction in the size of a population due to environmental events
such as earthquakes, floods, fires, disease, droughts, human genocide etc. Such events can reduce the
variation in the gene pool of a population. After an incident, a smaller population with few individuals,
with a correspondingly smaller genetic diversity, remains to pass on genes to future generations of
offspring. Such reduction population size results in the loss of genetic variation. The robustness of the
population is reduced; the ability of the population to survive is also reduced.
In other words, the higher the genetic variation or gene pool within a breeding population, the less
likely it is to suffer from inbreeding depression.
Mechanism responsible for inbreeding depression is the fitness advantage of heterozygous, which is
known as over dominance. This can lead to reduced fitness of a population with many homozygous
genotypes, even if they are not deleterious. Here, even the dominant alleles result in reduced fitness if
present homozygously.
Inbreeding can increase an individual’s inclusive fitness by producing young that share more of its
genome. Thus, when inbreeding has little or no genetic cost, there should be strong selective advantage
for inbreeding as well as recognition and cooperation among kin (Wilson 1976, May 1979). The cost of
inbreeding is therefore of theoretical importance as well.
Calculation of the total cost of inbreeding in natural population would involve considering the effects
of inbreeding on several components of fitness.
In small populations of randomly mating individuals, all may suffer from inbreeding depression
because of the cumulative effects of genetic drift that decrease the fitness of all individuals in the
population. Inbreeding depression may potentially be reduced, or purged, by breeding related
individuals. There can be several lethal consequences of inbreeding which include mortality, morbidity
and even it may lead to extinction.
Inbreeding depression in humans seems to be highly uncommon and not widely known, there have
been several cases of apparent forms of inbreeding depression in human populations. Charles Darwin through numerous experiments, was one of the first scientists to demonstrate the effects of inbreeding
depression. Charles’s wife, Emma was his first cousin. He attempted to study the theory of inbreeding
within his own children (Bittles 1991). Out of ten children, three died before the age of ten. Of the
rest, three had child-less long-term marriages.
A study has provided the evidence for inbreeding depression on cognitive abilities among children,
with high frequency of mental retardation among offspring in proportion to their increasing inbreeding
coefficients (Fareed and Afzal, 2014a). The depression on growth parameters (height, weight and body
mass index) due to inbreeding among children has revealed the significant increase in underweight
cases with increasing inbreeding coefficients (Fareed and Afzal, 2014b).
Reasons of Inbreeding
Studies have shown that in many societies consanguineous marriages predominate. In fact, in many
large populations of Asia and Africa twenty to fifty percent of all unions are that of consanguineous
marriages (Bittles 1991). There are several circumstances that would give a population a reason to
practice inbreeding at a large scale. Some of these reasons for practicing inbreeding include royalty,
religion and culture, casteism, socioeconomic class, geographic isolation and small population size.
Religion, culture and casteism can play a large role in the amount of inbreeding that takes place
in a population. In many Muslim and Hindu societies in Africa and Asia consanguious marriages,
especially unions of first cousins, account for twenty to fifty-five percent of the total. These religions
tend to inbreed because of religious acceptance, preference, and tradition. In many Indian tribes, the
cross cousin marriages are one of the preferential marriages. Moreover, the culture of these societies
also plays a large role to increased levels of inbreeding. Consanguineous marriages are thought to be
an advantage when considering compatibility of the bride and her husband’s family. This is
particularly important when discussing the bride’s relationship with her mother-in-law and the up-keep
of the family’s property. Another incentive to close relative marriages concerns bride wealth and
dowry. Consanguineous marriages can lead to greatly reduced or no payments at all in unions of this
culture. This allows small landowning families to keep their property and land (Bittles 1991).
Other groups that are associated with inbreeding because of religion and culture are the small
Anabaptist populations in North America. These groups include the Amish, the Mennonites, and the
Hutterites. These groups settled in North America in the 18th and 19th centuries in search of religious
freedom. These populations have shown increases in consanguineous marriages over time, and
reached to 85% in the 1950’s. The reason for the high levels of inbreeding is not only due to religion; it
can also be attributed to the small isolated farming communities in which these populations find
themselves. These factors of religion and small communal societies lead to limited choices when
searching for possible mates (Agarwala 2001). Studies show that inbreeding levels can depend largely
on geographic, demographic, social, and economic factors (Fuster 2001). Furthermore, numerous
other studies have shown that socioeconomic status can have a large impact on the level of
inbreeding. In many cases the poorest and least educated members of a community tend to have the
highest inbreeding levels in a population (Bittles 1991)
Inbreeding has also been seen to occur frequently in many royal families. Royal incest was commonly
found in Ancient Egyptian, Incan, Hawaiian, and many European royal families. Brother-sister unions
become more frequent when royalty is the major factor concerning the incidence of inbreeding. There
are several factors that can explain why royalty leads to high levels of inbreeding. One factor is that
the king has limitless power in many cultures, and he can do what he wants and marry who he
wants. Also, in many cases inbreeding is practiced in royal families to preserve royal blood
lines. Another explanation is that a royal family can keep land, material possessions and resources
within the family. Moreover, brother-sister royal incest allows succession of the throne to both a male
and female blood line. There are also cases in which royal incest is part of a culture and is sometimes
linked to legends or myths. One of the best documented cases of this was seen in the Incan culture in
the 16th century. The Incan king was to marry his full sister (Van Den Berghe 1980).
Royalty also uses inbreeding to try to maximize fitness. One of the royal strategies to
maximize fitness by using inbreeding to put as close to a genetic clone as possible on the throne as the
heir. Moreover, females tend to maximize fitness by picking the best possible mate, which in this case
would mean marrying to a higher social class. This leads to women with the highest-status in a
population to being the most inbred in this type of society (Van Den Berghe 1980).
Some classical examples of Inbreeding and its deleterious effect
European Royal Families
Inbreeding was very common among the royal families of Europe, and it has been linked as
the cause of the widespread number of cases of hemophilia in the families. The presence of
haemophilia in the royalty of Europe started with Queen Victoria of England. Victoria is thought to
be the original carrier for the recessive X-linked hemophilia gene, which lead to over twenty
members of royal families inheriting the disease in just over 100 years.
No ancestor of Queen Victoria showed any evidence of hemophilia, so several theories arose on the
gene’s origin. One theory is that Victoria was the victim of a mutation that could have been due to
years of inbreeding in British royalty. Another interesting theory is that Victoria’s mother had an affair
because of the intense pressure of producing an heir, and the Edward Duke of Kent was not Victoria’s
biological father (Stevens 1991).
Study on Japanese Children after WWII
Shortly after the United States dropped two atomic bombs on Japan in World War II there was an
increase in the number of consanguineous marriages in the areas surrounding Hiroshima
and Nagasaki. The most common union was seen to be inbreeding at the first-cousin level. The study
was set up to study some of the possible effects of inbreeding. The five effects of inbreeding looked at
in this study was: the fertility of the marriages, the mortality of the offspring, the morbidity of the
offspring, the reproductive performance of the offspring, and the characteristics of the offspring.
In the study, it was seen that inbreeding did not have an adverse effect on the fertility of the marriages,
but there were some significant increases seen on childhood mortality in the first year of life. Inbreeding also increased morbidity in the study. There were significant increases in levels of handicapped offspring associated with inbreeding (Schull 1965).
The Hutterites
The Hutterites are a small group of Anabaptists that fled Europe and Russia and settled in what is now
the Dakotas and Canada to escape from religious persecution. The Hutterites settled on communal
farms, which isolated them from outside populations. Their isolation along with their beliefs leads to a
highly inbred population. Moreover, the Hutterites are a good population to study because, like the
Amish, they keep very detailed genealogical records. The Hutterites are also among the most fertile
populations that commonly practice inbreeding (Ober 1999).