Imprinting is the deactivation of a locus in gametes of only one sex. A maternally imprinted locus has inactive maternal alleles; a paternally imprinted locus has inactive paternal alleles. Nonimprinted genes express both maternal and paternal alleles. Some imprinted regions contain a single gene, while other imprinted regions contain multiple genes. Imprinting deactivates via chromatin alteration: covalent modification of DNA, such as cytosine methylation to form 5-methyl-cytosine; and/or modification or substitution in chromatin of specific histone types.
Imprinting occurs during
gametogenesis and is a reversible process; it does not change the DNA sequence nor is it a mutation. Thus, a female carrying a paternal imprint will switch the imprint when passing it on to her offspring. Similarly, a male carrying a maternal imprint will switch the imprint when passing it on to his offspring. This conversion is controlled by
imprinting centers within imprinted regions. Imprinting centers initiate the epigenetic (non-mutation) change in the genome that eventually leads to condensation of the entire imprinted region.
Androgenetic embryos have an overlarge placenta but diminished fetal growth. Gynogenetic embryos have a diminished placenta and fetal growth thus arrests. This pattern is likely due to the male’s evolutionary drive to have powerful progeny, and the female’s need to conserve her own bodily resources. Genetic diseases involving imprinting include
Prader-Willi Syndrome and
Angelman Syndrome. In these cases, the patient inherits two imprinted chromosomes (or parts) from the same parent. An entire chromosome segment is thus unexpressed.
| Inheritance |
Genomes |
Outcome |
| Biparental |
Maternal and paternal genomes. |
Normal development. |
| Gynogenetic |
Two maternal genomes. |
Small placenta causes halt of embryonic development. |
| Androgenetic |
Two paternal genomes. |
Embryonic growth retarded. |
For most diploid species, sex is determined by one of the homologous pair of sex chromosomes. In humans and fruit flies, the sex chromosomes are X and Y (XX=female ; XY=male). In birds, female is WZ and male is ZZ. There are many ways of determining sex:
- Sex chromosome: humans, silkworms, drosophila, nematodes.
- Ploidy: bees, wasps, and ants.
- Environment: bonellia (sea worm larvae are undifferentiated; if lands on ocean floor, becomes female; if lands on female, becomes male).
Since in humans, Y chromosome carries very little genetic information, sex-linked genes usually refer to X-linked genes (genes on X chromosome). To determine if a gene is sex-linked, you perform pedigree analysis, use Drosophila, or perform a reciprocal cross.
Also known as the testes-determining gene or sex-determining region on the Y chromosome, SRY is a gene located on the short arm of the Y chromosome and encodes a DNA-binding transcription factor known as testes-determining factor (TDF) early (and briefly) in development. Although SRY does not determine sex in all cases — it is not present in 10% of unambiguous XX males — it is a key instrument in the concert of sex determination.
The LOD score (aka Z) gives an estimation of how closely two loci are linked (for example, a marker locus and a disease locus) and quantitates sample size (data reliability). A LOD score less than 2.0 means the two loci are not linked; a LOD score between 2.0 and 3.0 is inconclusive; and a LOD score greater than 3.0 strongly indicates linkage. Lod scores are always reported in association with the recombination frequency θ (theta), measured in Morgans, which describes linkage without taking into account sample size.
| Step |
Description |
| Step 1 |
Look at nothing more than affected/unaffected individuals and determine the mode of inheritance. |
| Step 2 |
Cross out individuals who cannot be identified as recombinants or nonrecombinants (uninformative individuals).
- Persons whose parents are not shown.
- Individuals without at least one heterozygous parent.
- Children are uninformative when the child and both parents have the same haplotype.
- If the allele of interest is dominant, then children with a homozygous recessive parent.
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| Step 3 |
Determine whether each informative individual is recombinant or nonrecombinant. Considering an informative individual’s haplotype, is it consistent with their parent’s haplotype and the mode of inheritance?
- Yes, consistent with parental haplotype -> Not Recombinant.
- No, inconsistent with parental haplotype -> Recombinant.
- Remember that even unaffected individuals can be recombinant!
|
| Step 4 |
Count how many recombinants and non-recombinants there are. |
| Step 5 |
- If you are provided a recombination frequency (θ, aka theta) then go straight to the equation below.
- If you are provided the gene-marker distance (measured in centimorgans or cM) then divide that value by 100 to calculate θ. For example, a marker 10cM from a gene yields a Θ of 10/100 = .10.
- If you are supposed to calculate the recombination frequency (θ), then use the equation below with θ values of .001, .10, .15, .20, .25, .30, .35, .40., .45 and .50. The correct θ value will yield the highest LOD Score.
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| Next Steps |
If these concepts are unclear, please review core concepts of linkage analysis and try a few problems. |
