inbreeding and human infertility Flashcards
what is inbreeding?
when individuals related
by ancestry reproduce. =
COSANGUINOUS MATINGS
what is IBD
the reduction/change in trait values that
occurs because of inbreeding.
what is F?
the probability that 2
individuals are identical by
descent (0.25 for siblings)
what is a lethal equivalent?
a recessive allele carried in
the heterozygous states that can be lethal in
the homozygous state.
how do you calculate the coefficient of IBD?
1-inbred trait
value/outbred trait value
what does inbreeding do to allelic and genotype frequencies?
does not change the allelic frquencies,but
does change genotype frequencies by
increasing homozygosity
why is increased homozygosity bad?
increased homozygosity increases
the likelihood of deleterious alleles
being expressed
what is dominance variance?
VD is a special type of variation which is found in populations containing dominant and recessive alleles for a particular gene.
Because dominant phenotypes are expressed by all genotypes possessing one or more dominant alleles, while recessive alleles are only expressed by double recessives, this cretes a difference between variation in genotype and phenotype, which affects natural selection
what are the necessary conditions for IBD?
for IBD, there must be dominance variance.
the fitness of the homozygotes minus the
heterozygotes must be
compare additive variance to dominance variance
when gene action is purely additive, the average
phenotypic effect associated with the alleles is
independent of the genetic background. with dominance,
effects change with genotype frequencies
is there any empirical evidence of IBD from dominance variance?
(Luo et al, 2001) - overdominant epistatic loci are the primary genetic basis of IBD & heterosis in rice grain yield components - 2 independent genes effected grain weight. the one that accounted for 68% of heterotic variation showed primarily non-additive gene action (overdominance). the overdominance resulted from epistatis from multilocus genotypes
(Rantala and Roff, 2007) found intersexual differences in dominance variance. what were they?
in the autumnal moth, there are intersexual differences in directional dominance for immune related genes. Inbred males did not differ much in immunocompetence to outbred males, but females did. in males, genetic variation for immune response is largely additive or non directional with respect to dominanace. in females, variation is much
reduced and consists of directional dominanace variance (Rantala and Roff, 2007)
how can the degree of directional dominance be explained by selection?
An allele having favourable fitness effects should go to fixation, and dominant deleterious alleles should be eliminated. however, deleterious recessive alleles will be maintained at low levels = directional dominance effect
why should directional dominance for traits weakly associated with fitness or under stabilising selection be low?
because mutations moving trait values up or down will be
selectively equivalent
decreased heterozygosity will lead to increased
expression of single gene recessive traits such as?
CF (autosomal); Tay sacks disease (autosomal); sickle cell anaemia (autosomal); Haemophilia (X linked); red-green colour blindness(x linked)
how do deleterious mutations get purged?
1)reduced population size/bottle neck effects expose
homozygous recessives
2)subsequent population increase with specific selection of depressed individuals = removal (purging) of deleterious mutations
how did o Grady et al 2005’s meta analysis predict that lethal equivalents would affect extinction risk?
did a metaanalysis to provide a comprehensive
estimate of IBD in natural wild bird and mammal populations. Found 12 lethal equivalents. in the analysis, these 12 L.E’s decreased time to extinction by up to 37%, even with purging. concluded that failure to provide accurate estimates of survival probabilities or gross over
estimations will endanger the survival propects of already scarce species
examples of inbreeding affecting disease risk ?
inbreeding increases susceptibility to pathogens in california sea lions, these sick individuals have higher than average parental relatedness and act as putative reservoirs for pathogens,contributing disproportionately to population pathogen load (Acavedo-Whitehouse et al, 2003)
can inbreeding ever be adaptive?
active inbreeding in cichlid fish has been documented. pairing between unfamiliar close kin is preferred over mating with non kin, because synchronous behaviour by parents is adaptive in raising offspring in species with biparental care. higher levels of care were found for inbreed couples than outbred couples and no evidence for inbreeding depression was found (Thunken et al, 2007)
how did (sherbourne et al, 2007) show that mice avoided inbreeding ?
house mice use a highly poly moprhic MUP major
urinary protein scent marker to avoid inbreeding
behaviour (Sherbourne et al, 2007)
what can inbreeding do to mating systems?
it can sometimes select for polyandry
how does fertility (amount of viable sperm) vary across taxa?
widespread and varying across and
within species: mouse 5%;goat
90%;gorilla 93%;human 10-90%
what did tone (1981) find out about DDT ?
in th 1970s, feminization of gull eggs led to female
biased sex ratios due to DDT from environmtenal
contamination (Toone, 1981)
what can the exposure to androgens do to fertility?
transient exposure of a gestating female rat during the period of gonadalsex determination to endocrine-disrupting chemicals androgens and oestrogens) induced and adult phenotype in the F1 generation of reduced spermatogenic capacity and increased male infertility. the effects on reproduction correlate with altered DNA methylation patterns in the germ line. this is an example of epigenetic
transgenerational actions of endocrine disruptors on male fertility (Anway et al, 2005)
what is the effective population size of humans?
humans have an effective population size of only ca
10,000. distance from subsaharan africa predicts
mutational load in diverse human genomes
what can chemical exposure do to amphibians?
exposure to the commonly used herbicide, Atrazine
caused gonadal retardation in frogs Rana pipiens in the
united states (hayes et al, 2002)
what are the conditions for sperm to fertilise an egg?
sperm are only able to penetrate the cervix mid-cycle.
they must be able to swim >25 microns p/sec. once in the uterus, they are moved by contractions to the UTJ.
the superior sperm (low DNA breakes and high membrane integrity) attach
how do we define infertility in humans?
the inbility to conceive
after 1 yr of trying regularly
how do males and females contribute to infertility cases?
24% of females experience difficulties. males
contribute to infertility in 30-50% of cases. approx
1000 IVF cycles per million europeans
how has sperm density changed in humans between 1930-1990?
Carlsen et al revealed that alarmingly, sperm density
decreased from ~ 120m/microlitre to just 40 between
1930-1990. there has been no such change in animals
over the same amount of time
what is ART?
Assisted reproductive technology (ART) is the technology used to achieve pregnancy in procedures such as fertility medication, artificial insemination, in vitro fertilization and surrogacy.
what is AI?
Artificial insemination involves sperm being placed into a female’s uterus (intrauterine) or cervix (intracervical) using artificial means rather than by sexual intercourse. This can be a very low-tech process, performed at home by the woman alone or with her partner
what is a conception cap?
conception cap may be used to aid conception by enhancing the natural process. Conception caps are used by placing semen into a small conception cap, then placing the cap onto the cervix. This holds the semen at the cervical os, protecting the semen from the acidic vaginal secretions and keeping it in contact with the cervical mucus.
What are the problems with ART?
ovarian stimulation may effect sons
multiple births - and twins tend to be less healthy
Intracytoplasmic sperm injection (ICSI, pronounced /ɪksiː/, IK-see) is an in vitro fertilization procedure in which a single sperm is injected directly into an egg. What are the problems with this?
icsi could in theory replace the fertilisation process and remove selection pressure for traits associated with insemination - e.g. acrosome characteristics (bypasses natural selection)
what can happen to sperm in ICSI?
DNA denaturation, chromatin damage. can result in early pregnancy loss (Zini et al, 2005).
when can inbreeding effects be masked in wild populates?
(Coltman et al, 1999) report significant inbreeding depression in survival of Soay sheep on St Kilda . Intestinal nematodes mediated the inbreeding effect because more homozygous Soay sheep suffered higher rates of parasitism and, in turn, lower overwinter survival than did heterozygous sheep. Sheep relieved temporarily of their parasite burden with anthelminthic drugs showed no association between heterozygosity and survival. Inbreeding effects thus appear as parasite-induced deaths in that population.
which traits are most effected by inbreeding?
Drosophila consistently experience more inbreeding
depression in fertility than in viability (Simmons et al, 1978). Fitness traits exhibit more inbreeding depression than do
morphological traits among animal species, perhaps
reflecting larger directional dominance in fitnessrelated
traits (DeRose & Roff, 1999) . Fitness-related traits might also be influenced by more loci (Houle, 1992).
