Linkage Disequilibrium
Definition
The non-random association of alleles at different loci within a population. Certain HLA allele combinations (e.g., HLA-A1 with HLA-B8 with HLA-DR3) occur at higher frequency than expected by chance. Linkage disequilibrium must be accounted for when calculating combined haplotype frequencies in forensic statistics.
- Definition
- Non-random association of alleles at different loci
- Example system
- HLA (e.g., HLA-A1 with HLA-B8 with HLA-DR3)
- Forensic relevance
- Must be accounted for in combined haplotype frequencies
- Contrast
- Independent loci allow simple multiplication of frequencies
Common questions
Why does linkage disequilibrium complicate forensic statistics?+
The standard product rule multiplies allele frequencies across independent loci to get a combined profile frequency, but that shortcut is invalid when alleles at different loci are not inherited independently. Linked HLA combinations occurring more often than chance would predict mean the combined frequency must be estimated from observed haplotype data rather than simple multiplication.
Is linkage disequilibrium the same thing as physical linkage on a chromosome?+
Not exactly. Physical linkage refers to loci being close together on the same chromosome, which tends to produce disequilibrium because they are inherited together, but disequilibrium can also arise between unlinked loci through population history, such as admixture or selection, without physical proximity.
How do labs handle linkage disequilibrium for STR loci used in standard DNA profiling?+
The core STR loci used in forensic profiling are deliberately chosen from different chromosomes or distant chromosomal regions specifically to minimise linkage disequilibrium, allowing the product rule to be applied with reasonable confidence. HLA and other closely linked systems require different, haplotype-based statistical treatment.
Related terms
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- Antiserum
- Serum collected from an immunised animal containing antibodies directed against a specific antigen or group of antigens. In species identification, antiserum raised...
- Blood Group System
- A set of red cell surface antigens encoded by one gene locus or by two tightly linked loci. The International Society of...
- Complement-Dependent Cytotoxicity (CDC)
- A serological HLA typing method in which test lymphocytes are incubated with HLA-specific antibody and then with complement. If the antibody binds,...
- Conditional Probability
- The probability of event A given that event B has already occurred, written P(A|B). Conditional probability is the basis of the multiplication...
- Hardy-Weinberg Equilibrium
- A condition in a population where genotype frequencies at a single locus conform to expectations derived from allele frequencies alone, assuming random...
- HLA Haplotype
- The specific combination of HLA alleles inherited as a block on one copy of chromosome 6. Because HLA loci are tightly linked,...
- HLA (Human Leukocyte Antigen)
- Cell-surface glycoproteins encoded by the major histocompatibility complex (MHC) on chromosome 6p21. They present peptide antigens to T cells and are the...
- Multiplication Rule
- For any two events: P(A and B) = P(A) x P(B|A). When A and B are independent, this simplifies to P(A) x...
- Paternity Index (PI)
- A likelihood ratio that compares the probability of the observed serological profile if the alleged father is the biological father to the...
- Phenotype Frequency
- The proportion of a given population that expresses a particular antigen combination. Multiplying phenotype frequencies across independent loci gives the combined frequency...
- Positive Dependence
- Events are positively dependent when the occurrence of one increases the probability of the other: P(A|B) > P(A). In this case P(A...
Explained in these topics
- Conditional Probability and IndependenceA statistical association between alleles at different genetic loci in a population. If two loci are in linkage disequilibrium, allele combinations at those lo...
- The HLA System and Its Role in Forensic Relationship Testing
- Minor Blood Group Systems: MNS, Kell, Duffy, and OthersA non-random association between alleles at different loci in a population. Within the MNS system, the M/N and S/s loci are physically close, so certain combin...