proteins therefore do not bind to red blood cells; they operate independently. instead of transporting co2 from the proteins of human red blood cells, c. elegan’s rh proteins transport nh3 out of its body. population data according to a comprehensive study, the worldwide frequency of rh-positive and rh-negative blood types is approximately 94% and 6%, respectively. the same study concluded that the share of the population with rh-negative blood type is set to fall further in the future primarily due to low population growth in europe. the frequency of rh factor blood types and the rhd neg allele gene differs in various populations. population data for the rh d factor and rhd neg allele population rh(d) neg rh(d) pos rh(d) neg alleles african americans ∼ 7% 93% ∼ 26% albania 10.86% 89% weak d 1.4% basques 21%–36% 65% ∼ 60% britain 17% 83% china < 1% > 99% ethiopians 1%–21% 99%–79% europeans (others) 16% 84% 40% india 0.6%–8.4% 99.4%–91.6% indonesia < 1% > 99% japan < 1% > 99% koreans < 1% > 99% madagascar 1% 99% moroccans 9.5% 90.5% moroccans (high atlas) ∼ 29% 71% native americans ∼ 1% 99% ∼ 10% nigeria 6% 94% saudi arabia 8.8% 91.2% 29.5% subequatorial africa 1%–3% 99%–97% united states 15% 85% genetics this is a punnett square for rh factor inheritance. this square specifically shows two heterozygous rh positive parents and the possible genotypes/phenotypes the offspring could have. the d antigen is inherited as one gene (rhd) (on the short arm of the first chromosome, p36.13–p34.3) with various alleles. typically, rhesus positive people have an intact rhd gene while negative people lack the gene (or have mutations in it). however, there are exceptions: for instance, japanese and black africans may have an intact gene that is not expressed or only at very low levels. the gene codes for the rhd protein on the red blood cell membrane. d− individuals who lack a functional rhd gene do not produce the d antigen, and may be immunized by d+ blood. the d antigen is a dominant trait. if both of a child's parents are rh negative, the child will definitely be rh negative. otherwise the child may be rh positive or rh negative, depending on the parents' specific genotypes. the epitopes for the next 4 most common rh antigens, c, c, e and e are expressed on the highly similar rhce protein that is genetically encoded in the rhce gene, also found on chromosome 1. it has been shown that the rhd gene arose by duplication of the rhce gene during primate evolution. mice have just one rh gene. the rhag gene, which is responsible for encoding rh-associated glycoprotein (rhag), is found on chromosome 6a. the polypeptides produced from the rhd and rhce genes form a complex on the red blood cell membrane with the rh-associated glycoprotein. function blood group rh c/e/d polypeptideidentifierssymbol?interproipr002229 on the basis of structural homology it has been proposed that the product of rhd gene, the rhd protein, is a membrane transport protein of uncertain specificity (co2 or nh3) and unknown physiological role. the three-dimensional structure of the related rhcg protein and biochemical analysis of the rhd protein complex indicates that the rhd protein is one of three subunits of an ammonia transporter. three recent studies have reported a protective effect of the rhd-positive phenotype, especially rhd heterozygosity, against the negative effect of latent toxoplasmosis on psychomotor performance in infected subjects. rhd-negative compared to rhd-positive subjects without anamnestic titres of anti-toxoplasma antibodies have shorter reaction times in tests of simple reaction times. and conversely, rhd-negative subjects with anamnestic titres (i.e. with latent toxoplasmosis) exhibited much longer reaction times than their rhd-positive counterparts. the published data suggested that only the protection of rhd-positive heterozygotes was long term in nature; the protection of rhd-positive homozygotes decreased with duration of the infection while the performance of rhd-negative homozygotes decreased immediately after the infection. the overall change in reaction times was always larger in the rhd-negative group than in the rhd-positive. rhd polymorphism origin of rhd polymorphism for a long time, the origin of rhd polymorphism was an evolutionary enigma. before the advent of modern medicine, the carriers of the rarer allele (e.g. rhd-negative women in a population of rhd positives or rhd-positive men in a population of rhd negatives) were at a disadvantage as some of their children (rhd-positive children born to preimmunised rhd-negative mothers) were at a higher risk of fetal or newborn death or health impairment from hemolytic disease. natural selection aside, the rhd-rhce region is structurally predisposed to many mutations seen in humans, since the pair arose by gene duplication and remain similar enough for unequal crossing over to occur. in addition to the case where d is deleted, crossover can also produce a single gene mixing exons from both rhd and rhce, forming the majority of partial d types.: 323 weak d comparison weak dpartial d change in d decreased amountstructural alternation can donateas if being: d positived positive can receive bloodas if being: d positive (usually)d negative in serologic testing, d positive blood is easily identified. units that are d negative are often retested to rule out a weaker reaction. this was previously referred to as du, which has been replaced.: 322 by definition, weak d phenotype is characterized by negative reaction with anti-d reagent at immediate spin (is), negative reaction after 37 °c incubation, and positive reaction at anti-human globulin (ahg) phase. weak d phenotype can occur in several ways. in some cases, this phenotype occurs because of an altered surface protein that is more common in people of european descent. an inheritable form also occurs, as a result of a weakened form of the r0 gene. weak d may also occur as "c in trans", whereby a c gene is present on the opposite chromosome to a d gene (as in the combination r0r', or "dce/dce"). the testing is difficult, since using different anti-d reagents, especially the older polyclonal reagents, may give different results. the practical implication of this is that people with this sub-phenotype will have a product labeled as "d positive" when donating blood. when receiving blood, they are sometimes typed as a "d negative", though this is the subject of some debate. most "weak d" patients can receive "d positive" blood without complications.: 323 however, it is important to correctly identify the ones that have to be considered d+ or d−. this is important, since most blood banks have a limited supply of "d negative" blood and the correct transfusion is clinically relevant. in this respect, genotyping of blood groups has much simplified this detection of the various variants in the rh blood group system. partial d it is important to differentiate weak d (due to a quantitative difference in the d antigen) from partial d (due to a qualitative difference in the d antigen). simply put, the weak d phenotype is due to a reduced number of d antigens on a red blood cell. in contrast, the partial d phenotype is due to an alteration in d-epitopes. thus, in partial d, the number of d antigens is not reduced but the protein structure is altered. these individuals, if alloimmunized to d, can produce an anti-d antibody. therefore, partial d patients who are donating blood should be labeled as d-positive but, if receiving blood, they should be labeled as d-negative and receive d-negative units. in the past, partial d was called 'd mosaic' or 'd variant.' different partial d phenotypes are defined by different d epitopes on the outer surface of the red blood cell membrane. more than 30 different partial d phenotypes have been described. rhnull phenotype rhnull individuals have no rh antigens (no rh or rhag) on their red blood cells. this rare condition has been called "golden blood". as a consequence of rh antigen absence, rhnull red blood cells also lack lw and fy5 and show weak expression of s, s, and u antigens. red blood cells lacking rh/rhag proteins have structural abnormalities (such as stomatocytosis) and cell membrane defects that can result in hemolytic anemia. the first rhnull blood was discovered in an aboriginal australian woman, in 1961. only 43 individuals have been reported to have it worldwide. only nine active donors have been reported. its properties make it attractive in numerous medical applications, but scarcity makes it expensive to transport and acquire. other rh group antigens as of 2023, over 50 antigens have been described in the rh group system; among those described here, the d, c, c, e and e antigens are the most important. the others are much less frequently encountered or are rarely clinically significant. each is given a number, though the highest assigned number (cevf or rh61 according to the isbt terminology) is not an accurate reflection of the antigens encountered since many (e.g. rh38) have been combined, reassigned to other groups, or otherwise removed.: 324 some of the other rh "antigens" are f ("ce", rh6), ce (rh7), cw (rh8), cx (rh9), v (rh10), ew (rh11), g (rh12), tar (rh40), vs (rh20), dw (rh23), and ce (rh22). some of these groups, including f, ce and ce, describe grouping of some existing groups. others, like v, describe an epitope created by some other mutation on the rhd and rhce genes. v in particular is caused by a mutation on rhce. history the term "rh" was originally an abbreviation of "rhesus factor". it was discovered in 1939 by karl landsteiner and alexander s. wiener, who, at the time, believed it to be a similar antigen found in rhesus macaque red blood cells. it was subsequently discovered that the human factor is not identical to the rhesus monkey factor, but by then, "rhesus group" and like terms were already in widespread, worldwide use. thus, notwithstanding it is a misnomer, the term survives (e.g., rhesus blood group system and the obsolete terms rhesus factor, rhesus positive, and rhesus negative – all three of which actually refer specifically and only to the rh d factor and are thus misleading when unmodified). contemporary practice is to use "rh" as a term of art instead of "rhesus" (e.g., "rh group", "rh factors", "rh d", etc.). the significance of their discovery was not immediately apparent and was only realized in 1940, after subsequent findings by philip levine and rufus stetson. the serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. the antigen that induced this immunization was designated by them as rh factor to indicate that rhesus blood had been used for the production of the serum. in 1939, phillip levine and rufus stetson published in a first case report the clinical consequences of non-recognized rh factor, hemolytic transfusion reaction, and hemolytic disease of the newborn in its most severe form. it was recognized that the serum of the reported woman agglutinated with red blood cells of about 80% of the people although the then known blood groups, in particular abo were matched. no name was given to this agglutinin when described. in 1940, karl landsteiner and alexander s. wiener made the connection to their earlier discovery, reporting a serum that also reacted with about 85% of different human red blood cells. in 1941, group o: a patient of dr. paul in irvington, nj, delivered a normal infant in 1931; this pregnancy was followed by a long period of sterility. the second pregnancy (april, 1941) resulted in an infant with icterus gravis. in may 1941, the third anti-rh serum (m.s.) of group o became available. based on the serologic similarities, rh factor was later also used for antigens, and anti-rh for antibodies, found in humans such as those previously described by levine and stetson. although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term "rh" was kept for the clinically described human antibodies which are different from the ones related to the rhesus monkey. this real factor found in rhesus macaque was classified in the landsteiner-weiner antigen system (antigen lw, antibody anti-lw) in honor of the discoverers. it was recognized that the rh factor was just one in a system of various antigens. based on different models of genetic inheritance, two different terminologies were developed; both of them are