Genetic Anticipation, Linkage Disequilibrium, and Mate Selection

• Manic Traits: An EP/SB Description by James Brody, 4/5/97
  
  

Genetic Anticipation, Linkage Disequilibrium, & Mate Selection

I recently attended the 11th Annual Mood Disorders: Research/Education Symposium, sponsored by the Johns Hopkins Affective Disorders Clinic & the Depression and Related Affective Disorders Association. Christopher Ross, MD, PhD, spoke about genetic foundations of Huntingtons Chorea with some reference to bipolar disorder. It was hours and miles later that I connected one of his concepts with one of Fisher & Land (as described in Dawkins, R, 1987, The Blind Watchmaker, NY: Norton, pp 202-206). Ross used the concept of "Anticipation"; Fisher and others gave us "Linkage Disequilibrium." Both concepts may describe similar events and have implications for evolution, epidemiology, and the treatment of genetically influenced disorders.

"Anticipation" describes a phenomenon (the earlier onset and greater severity of the disorder across generations) associated with Huntingtons Chorea. The mean age of onset is about 42 yrs with a range of 19-82 yrs in male or female parents. If the disorder is transmitted through the father, the onset drops to 35 yrs for sons or daughters (if through the mother, then age of onset does not change). Earlier onset has been correlated with a more severe course of the disorder. It has also been correlated with a DNA change called "Trinucleotide Repeat Expansion." That is, fixed Cytosine-Adenine-Guanine sequences are repeated in seriatum on the gene; fewer than 30 repetitions is correlated with a normal developmental course; more than 36 is correlated with Huntingtons. The greater the number of repeats, the earlier the onset of illness. (Ross suggested this model may also apply to bipolar disorder.)

"Linkage Disequilibrium" accounts for a rapid increase in the size of physical characteristics (such as antlers, peacock tails, giraffe necks, or tail feathers) thought to be attractive in mating. A male bird with a long tail is usually the product of aother male bird with a long tail. It's also likely that his mother was attracted to males with long tails because she mated with one. Thus, the son carries not only material (from his dad) that gives him sons with a long tail but also material (from his mother) that gives him daughters that will be attracted to long tailed males. Because of the tendency for an "attraction" to be carried in the same bird as the physical trait, "linkage" is assumed. "Disequilibrium" applies because rapid increases in secondary sexual traits can occur in just a few generations.

Field birds do not mate randomly; neither do people. (See Mash E & Barkley R, 1996, Child Psychopathology, NY: Guilford, for material about genetic influences in each of the chapters. Non-random mate selection appears to be a factor in a wide range of the impulse, anxiety, and depressive disorders. a factor in a wide range of the impulse, anxiety, and depressive disorders. Kay Jamison has remarked that people with bipolar disorder have a tendency to mate with people similarly afflicted.) Linkage disequilibrium has a subtle twist that differs from simple assortative mating. That is, we may prefer (fall in love with) people who are not necessarily like us but like our parents or grandparents.(1)

The tradition of "romantic" love may be due to and may encourage Linkage Disequilibrium effects; it may also encourage "Anticipation" effects in Huntingtons. The concepts may be different aspects of common processes. Trinucleotide Triplet Expansion could be a mechanism for both of these phenomena. In any event, the female role should be the crucial one. Males change over time (evolutionary and ontogenetic) to female standards. Trivers' notions of parental investment could apply in that females generally seek males who are healthy, resourceful, and apt to be around to rear the children. Psychological, physical, or behavioral familiarity may be a signal that the male is predictable and in comfortable ways for the female.(2) However, females of many species often have affairs with males (large, flashy, or wealthy males) other than their mate. Making realistic information available to women about varied disorders and heritability might be effective given that you would be matching their wishes for healthy children against their feelings of love and attachment to a particular male in their future, but one with a disability.

NOTES:

1) The concept of imprinting may also have relevance. It has been applied to mate selection in geese (See Todd PM, 1996, Sexual Selection & the Evolution of Learning, in Belew R & Mitchell M, Eds, Adaptive Individuals in Evolving Populations: Models and Algorithms, Reading MA: Addison Wesley). Imprinting could also be a mechanism in human mate choice. Thus, if you grow up with a bipolar (or Huntingtons) parent, you may be more comfortable with bipolar (or Huntingtons) partners. Research will have to dissect further whether early adoptees more closely resemble their natural or adopted parents. So far, the data seem to favor the natural parents and natural grandparents as the larger influence on subsequent emotional or behavioral difficulties. More later.

2) Or uncomfortable ways. Betty, referring to her husband, commented that "I married my father and it took me three years to realize it. I got furious, I can't stand either one of them, I'm still mad!"

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