Stem Cell Donor Matching for Patients of Mixed Race

Stem Cell Donor Matching for Patients of Mixed Race

21 pages

Ted Bergstrom, Aaron and Cherie Raznick Chair of Economics
University of California, Santa Barbara

Rod Garratt, Professor of Econommics
University of California, Santa Barbara

Damien Sheehan-Connor, Assistant Professor of Economics
Wesleyan University

The plight of multiracial leukemia patients who are unable to find matching stem cell donors has received much media attention. These news stories, while dramatic, are short on statistical information and long on misconceptions. We apply simple probability theory, the genetics of sexual diploid reproduction, and the theory of public goods to produce estimates of the probabilities that multiracial patients will find matching donors in the existing registry. We then compute the benefits and costs of registering more potential donors of single and mixed races.

…4.1 The concept of race

The racial categories, white, African-American, Asian-American, and Hispanic into which NMDP registrants are sorted is coarse and somewhat arbitrary. Since the recorded race of a registrant is self-declared, it indicates a social construction that does not necessarily correspond to genetic inheritance. Statistics show, however that the distribution of HLA types differs markedly between races.  For example, the probability that a randomly selected white American will match another randomly selected white is 34 times that of matching a random Asian-American, 16 times that of matching a random African-American, and 6 times that of matching a random Hispanic. These distributional differences have important implications for recruitment of registrants from racial minorities.

Our statistical measurements are built on the Kollman et al [11] estimates of haploid distributions within each race. Kollman’s estimates, like those in the earlier study by Mori et al [13], are founded on a model that makes two critical assumptions about marriage patterns.  The first assumption is that each racial group is endogamous, that is marriage occurs almost entirely within races. The second assumption is that conditional on marrying within group, the probability that two people marry is independent of their HLA types.

Since the social construct of race is more likely to influence marriage patterns than genetic classification, the use of self-declared race to determine categories seems appropriate for the model that is being estimated. Jacobs and Labov [6] collected data on all married heads of households and their spouses from a 1 percent sample of the 1990 U.S. Census. They determined the self-declared race or national origin of each member of each couple. They found that almost 98 percent of marriages of whites and 96 percent of marriages of African-Americans were endogamous. The Jacobs-Labov study shows that approximately 85 percent of Asian-Americans are married to other Asian-Americans and 77 percent of Hispanics are married to other Hispanics.67  The genetic composition of the current population depends, of course, on the marriage patterns of their parents’ generation, not on current marriage patterns. There is good reason to believe that the current population of Asian-Americans and of Hispanics are children of more endogamous populations than is indicated by current marriages. About 2/3 of the existing population of Asian-Americans were born in Asia and their ancestors for many generations would have had little exposure to non-Asians. About 1/3 of the existing population of Hispanics are immigrants from regions where the population is almost entirely Hispanic…

…A similar diffculty is found with “Hispanic” as a racial category. The Hispanic population of the United States includes significant subpopulations that differ in ethnic makeup and have had little contact with each other for many generations. About 66 percent of the Hispanic population of the United States is of Mexican extraction, 13 percent come from Central and South America, 9 percent are Puerto Rican, and 4 percent are of Cuban extraction. Genetic admixture studies of Hispanics in the U.S. reveal that Mexican-Americans on average have 30-40 percent Native American ancestry, while immigrants from the Spanish Caribbean have African genetic contributions that range from 20-40 percent and contributions of about 18 percent from the native American Arawaks and Caribs

…Although current rates of intermarriage between African-Americans and whites are low, African-Americans carry a significant amount of genetic material obtained from white ancestors. As Kittles et al [8] observes, “The vast majority of contemporary African Americans are descendants of enslaved Africans kidnapped and transported to America during the transatlantic slave trade from 1619 to 1850.” During the period of slavery, there was substantial mixing of the white and African-American gene pool. Kittles et al reports that it is estimated that in 1860, “there were 4.5 million people of African descent in the U.S., of which 600,000 were of mixed ancestry or “mulattos”.

Geneticists have developed methods for using genetic markers to estimate admixture proportions, that is the proportions of genetic material in a single population that is inherited from members of two or more distinct ancestral populations. Several studies have estimated admixture proportions from samples of African-Americans. These studies indicate that the percentage of European admixture in the African-American population differs substantially by region, ranging from 3.5 percent in the Gullah sea island community of South Carolina, 10 percent in the rural South, about 20 percent in the industrial North, and 22-35 percent on the West Coast. [8](Figure 2), [14] The admixture of African-American genetic material in the U.S. white population appears to be much smaller. The geographic differences in the genetic makeup of the African-American population suggests that the accuracy of estimations of HLA-distributions for African Americans could be improved by disaggregating according to region of birth…

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