A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study

A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD.     

Rationale and design of the Leipzig (LIFE) Heart Study: phenotyping and cardiovascular characteristics of patients with coronary artery disease

Objective

We established the Leipzig (LIFE) Heart Study, a biobank and database of patients with different stages of coronary artery disease (CAD) for studies of clinical, metabolic, cellular and genetic factors of cardiovascular diseases.

Design

The Leipzig (LIFE) Heart Study ({"type":"clinical-trial","attrs":{"text":"NCT00497887","term_id":"NCT00497887"}}NCT00497887) is an ongoing observational angiographic study including subjects with different entities of CAD. Cohort 1, patients undergoing first-time diagnostic coronary angiography due to suspected stable CAD with previously untreated coronary arteries. Cohort 2, patients with acute myocardial infarction (MI) requiring percutaneous revascularization. Cohort 3, patients with known left main coronary artery disease (LMCAD).

Results

We present preliminary results of demographics and phenotyping based on a 4-years analysis of a total of 3,165 subjects. Cohort 1 (n = 2,274) shows the typical distribution of elective coronary angiography cohorts with 43% cases with obstructive CAD and 37% normal angiograms. Cohorts 2 and 3 consist of 590 and 301 subjects, respectively, adding patients with severe forms of CAD. The suitability of the database and biobank to perform association studies was confirmed by replication of the CAD susceptibility locus on chromosome 9p21 (OR per allele: 1.55 (any CAD), 1.54 (MI), 1.74 (LMCAD), p<10⁻⁶, respectively). A novel finding was that patients with LMCAD had a stronger association with 9p21 than patients with obstructive CAD without LMCAD (OR 1.22, p = 0.042). In contrast, 9p21 did not associate with myocardial infarction in excess of stable CAD.

Conclusion

The Leipzig (LIFE) Heart Study provides a basis to identify molecular targets related to atherogenesis and associated metabolic disorders. The study may contribute to an improvement of individual prediction, prevention, and treatment of CAD.     

A study of genetic linkage heterogeneity in 35 adult-onset polycystic kidney disease families

A genetic heterogeneity analysis of 35 kindreds with adult-onset polycystic kidney disease (ADPKD) was carried out using the D16S85, D16S84, D16S125 and D16S94 loci that are closely linked to the PKD1 locus on chromosome 16. The results show that the likelihood of two ADPKD loci is 2,514.9 times greater than for a single locus (P < 0.0001). The maximum likelihood lod score is 27.38 under heterogeneity with PKD1 lying 4.9 cM proximal to D16S85 (in males). At least 3% of kindreds are unlinked to PKD1, since the 95% confidence limits of alpha, the proportion of families linked to PKD1, are 0.54–0.97. Only 2 out of 35 kindreds (5.7%) show statistically significant evidence of non-linkage to PKD1, with conditional probabilities of 0.987 and 0.993 that the disease locus is unlinked. This confirms the existence of a small subgroup of ADPKD kindreds that are unlinked to PKD1 and provides a firm basis for genetic counselling of this population on the basis of DNA probes.     

A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics

Evidence of the existence of major prostate cancer (PC)–susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes. In this study, we explored two approaches to overcome this difficulty, in an analysis of a large number of families with PC in the International Consortium for Prostate Cancer Genetics (ICPCG). One approach was to combine linkage data from a total of 1,233 families to increase the statistical power for detecting linkage. Using parametric (dominant and recessive) and nonparametric analyses, we identified five regions with “suggestive” linkage (LOD score >1.86): 5q12, 8p21, 15q11, 17q21, and 22q12. The second approach was to focus on subsets of families that are more likely to segregate highly penetrant mutations, including families with large numbers of affected individuals or early age at diagnosis. Stronger evidence of linkage in several regions was identified, including a “significant” linkage at 22q12, with a LOD score of 3.57, and five suggestive linkages (1q25, 8q13, 13q14, 16p13, and 17q21) in 269 families with at least five affected members. In addition, four additional suggestive linkages (3p24, 5q35, 11q22, and Xq12) were found in 606 families with mean age at diagnosis of 65 years. Although it is difficult to determine the true statistical significance of these findings, a conservative interpretation of these results would be that if major PC-susceptibility genes do exist, they are most likely located in the regions generating suggestive or significant linkage signals in this large study.     

A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program

A combined analysis of genome scans for obesity was undertaken using the interim results from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. In this research project, four multicenter networks of investigators conducted eight individual studies. Data were available on 6,849 individuals from four ethnic groups (white, black, Mexican American, and Asian). The sample represents the largest single collection of genomewide scan data that has been analyzed for obesity and provides a test of the reproducibility of linkage analysis for a complex phenotype. Body mass index (BMI) was used as the measure of adiposity. Genomewide linkage analyses were first performed separately in each of the eight ethnic groups in the four networks, through use of the variance-component method. Only one region in the analyses of the individual studies showed significant linkage with BMI: 3q22.1 (LOD 3.45, for the GENOA network black sample). Six additional regions were found with an associated LOD >2, including 3p24.1, 7p15.2, 7q22.3, 14q24.3, 16q12.2, and 17p11.2. Among these findings, the linkage at 7p15.2, 7q22.3, and 17p11.2 has been reported elsewhere. A modified Fisher's omnibus procedure was then used to combine the P values from each of the eight genome scans. A complimentary approach to the meta-analysis was undertaken, combining the average allele-sharing identity by descent (pi) for whites, blacks, and Mexican Americans. Using this approach, we found strong linkage evidence for a quantitative-trait locus at 3q27 (marker D3S2427; LOD 3.40, P=.03). The same location has been shown to be linked with obesity-related traits and diabetes in at least two other studies. These results (1) confirm the previously reported obesity-susceptibility locus on chromosomes 3, 7, and 17 and (2) demonstrate that combining samples from different studies can increase the power to detect common genes with a small-to-moderate effect, so long as the same gene has an effect in all samples considered.     

Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group.

Among the numerous leukodystrophies that have an early onset and no biochemical markers, Pelizaeus-Merzbacher disease (PMD) is one that can be identified using strict clinical criteria and demonstrating an abnormal formation of myelin that is restricted to the CNS in electrophysiological studies and brain magnetic resonance imaging (MRI). In PMD, 12 different base substitutions and one total deletion of the genomic region containing the PLP gene have been reported, but, despite extensive analysis, PLP exon mutations have been found in only 10%-25% of the families analyzed. To test the genetic homogeneity of this disease, we have carried out linkage analysis with polymorphic markers of the PLP genomic region in 16 families selected on strict diagnostic criteria of PMD. We observed a tight linkage of the PMD locus with markers of the PLP gene (cDNA PLP, exon IV polymorphism) and of the Xq22 region (DXS17, DXS94, and DXS287), whereas the markers located more proximally (DXYS1X and DXS3) or distally (DXS11) were not linked to the PMD locus. Multipoint analysis gave a maximal location score for the PMD locus (13.98) and the PLP gene (8.32) in the same interval between DXS94 and DXS287, suggesting that in all families PMD is linked to the PLP locus. Mutations of the extraexonic PLP gene sequences or of another unknown close gene could be involved in PMD. In an attempt to identify molecular defects of this genomic region that are responsible for PMD, these results meant that RFLP analysis could be used to improve genetic counseling for the numerous affected families in which a PLP exon mutation could not be demonstrated.     

Genetic variation in lipoprotein (a) levels in families enriched for coronary artery disease is determined almost entirely by the apolipoprotein (a) gene locus.

Lipoprotein (a) (Lp[a]) is a cholesterol-rich lipoprotein resembling LDL but also containing a large polypeptide designated apolipoprotein (a) (apo[a]). Its levels are highly variable among individuals and, in a number of studies, are strongly correlated with the risk of coronary artery disease (CAD). In an effort to determine which genes control Lp(a) levels, we have studied 25 multiplex families (comprising 298 members) enriched for CAD. The apo(a) gene was genotyped among the families, using a highly informative pulse-field gel electrophoresis procedure. In addition, polymorphisms of the gene for the other major protein of Lp(a), apolipoprotein B (apoB), were examined. Quantitative sib-pair linkage analysis indicates that apo(a) is the major gene controlling Lp(a) levels in this CAD population (P = .001; 99 sib pairs), whereas the apoB gene demonstrated no significant quantitative linkage effect. We estimate that the apo(a) locus accounts for < or = 98% of variance of Lp(a) serum levels. Approximately 43% of this variation is explained by size polymorphisms within the apo(a) gene. These results indicate that the apo(a) gene is the major determinant of Lp(a) serum levels not only in the general population but also in a high-risk CAD population.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Summary Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099±0.014% for synaptophysin- and 0.037±0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin-and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide.When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as nonischemic myocardium.This study was supported by the SFB 320 within the Deutsche Forschungsgemeinschaft (DFG)Parts of the results were presented at the 59. Scientific Session of the American Heart Association (1986) and at the Congress of the Deutsche Gesellschaft für Herz- und Kreislaufforschung 1987.     

The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS)

Background

Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro.

Methods

To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin^® and the polycation transduction enhancer Transfectam^®. The EGFP-positive transduced cells were then enriched by flow cytometry.

Results

More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than in the co-cultures of non-transduced skeletal myoblasts with cardiac myocytes and similar to the rates in pure cultures of cardiac myocytes.

Conclusion

The observed elevated field action potential activation rate in the co-cultures of cardiac myocytes with connexin 43 transduced skeletal myoblasts indicates enhanced cell-to-cell electrical coupling due to overexpression of connexin 43 in skeletal myoblasts. This study suggests that retroviral connexin 43 transduction can be employed to augment engineering of the electrocompetent cardiac grafts from patients' own skeletal myoblasts.     

Leptin and coronary heart disease risk: prospective case control study of British women

Objective: Prospective studies have shown a positive association between leptin concentrations and coronary heart disease (CHD) in men, but its effect in women is unclear. Our objective was to examine the association of serum leptin levels with CHD in a prospective study of women. Research Methods and Procedures: We conducted a prospective (4 year) case (N = 165) control (N = 335) study nested within a cohort of 4286 British women. Results: With mutual adjustment for each other and age, social class, smoking, and physical activity, leptin was positively associated with BMI, fasting insulin, total cholesterol, low‐density lipoprotein‐cholesterol, triglycerides, and hypertension and was inversely associated with homeostasis model assessment insulin sensitivity. Leptin was not associated with CHD risk (age‐adjusted relative risk for a doubling of leptin: 1.08 [95% confidence interval (CI): 0.91, 1.29]). This changed little with adjustment for childhood and adult social class, smoking, alcohol, and physical activity but attenuated to 1.00 (95% CI: 0.80, 1.26) with further adjustment for other metabolic risk factors (waist‐to‐hip ratio, low‐density lipoprotein‐cholesterol, triglycerides, C‐reactive protein, fasting insulin, hypertension). Discussion: We found no strong statistical evidence that leptin is associated with CHD risk in this study population of older British women. Further research is needed to compare associations of leptin with CHD in men and women and to determine whether the effect varies by gender.     

Classification of flea families (Siphonaptera): I. Family Hystrichopsyllidae (first part)

A contribution is made to the previously elaborated classification of the order Siphonaptera (Medvedev, 1994, 1998). Host-parasite associations, geographical distribution, and morphology of the family Hystrichopsyllidae (sensu Hopkins and Rothschild, 1962, 1966) in comparison with other flea families are analyzed together with a position of the family within the infraorder Hystrichopsyllomorpha. The presence of two spermathecae, frequently used as a taxonomic character, is a character insufficient for the basic phylogenetic reconstructions, e.g., establishment of close relationship between the families Coptopsyllidae and Macropsyllidae or the tribes Ctenopariini and Hystrichopsyllini, because this character is a plesiomorphy of the order Siphonaptera. The subfamily Hystrichopsyllinae (sensu Hopkins and Rothschild, 1962) is characterized by a large number of morphological features which can be considered as plesiomorphic characters of the family Hystrichopsyllidae as a whole. The subfamily Hystrichopsyllinae should be restricted to the tribes Ctenopariini and Hystrichopsyllini. The family Macropsyllidae possesses a unique structure of the ctenidia and some other structures. It should be treated as a group closely related to Hystrichopsyllidae. The family Coptopsyllidae demonstrates another trend in the evolution of the head, thorax, and abdomen.     

A novel major histocompatibility complex locus confers the risk of premature coronary artery disease in a Chinese Han population

Several novel loci have been proved to be associated with coronary artery disease and/or myocardial infarction risk by genome-wide association studies, however, the available coronary artery disease risk variants explain only a small proportion of the predicted genetic heritability of the disease. Recently, a novel coronary artery disease locus on chromosome 6p21.3 in the major histocompatibility complex was identified in an European population. We hereby investigated whether this single nucleotide polymorphisms (rs3869109) confers the risk of premature coronary artery disease in a Chinese Han population. A total of 422 patients were studied including 210 cases with coronary stenosis ≥50 % or previous myocardial infarction (male <55 years and female <65 years) and 212 controls without documented coronary artery disease. Ligase detection reaction was performed to detect rs3869109. The 3 genotypes AA, AG, and GG were present in rs3869109. There were significant differences between the control and premature coronary artery disease groups in the frequencies of the rs3869109 variants and alleles (all P < 0.05). The distribution of 3 genotypes and alleles at rs3869109 does not differ between women and men (all P > 0.05). There was a significant association between rs3869109 genotypes and the severity of premature coronary artery disease (P = 0.038). Multivariate logistic regression showed that carriers with AG and GG genotypes at rs3869109 have a higher risk of premature coronary artery disease than carriers of AA genotype (odds ratio [OR] 1.997, 95 % CI: 1.166–3.419, P = 0.012; OR 1.695, 95 % CI: 1.044–2.752, P = 0.033; respectively). Our results indicate that the rs3869109 variants are associated with premature coronary artery disease in a Chinese Han population, suggesting this genetic risk marker is useful in early coronary artery disease risk prediction.     

Association of polymorphic marker G(-455)A of gene FGB with coronary artery disease

Patients with coronary artery disease (CAD), including those who have had myocardial infarction (MI), and control subjects have been compared with respect to the distributions of the alleles and genotypes of polymorphic marker G(-455)A of gene FGB encoding the fibrinogen beta-chain. The groups studied do not differ significantly with respect to the distributions of G(-455)A alleles and genotypes. This indicates that this marker is not associated with CAD in the Moscow population. Allele A of the G(-455)A polymorphic marker has been found to be associated with an increased fibrinogen content of blood plasma in women with CAD.     

Genetic effects on obesity assessed by bivariate genome scan: the Mexican-American coronary artery disease study

Objective: To identify the genetic determinants of obesity using univariate and bivariate models in a genome scan. Research Methods and Procedures: We evaluated the genetic and environmental effects and performed a genome‐wide linkage analysis of obesity‐related traits in 478 subjects from 105 Mexican‐American nuclear families ascertained through a proband with documented coronary artery disease. The available obesity traits include BMI, body surface area (BSA), waist‐to‐hip ratio (WHR), and trunk fat mass as percentage of body weight. Heritability estimates and multipoint linkage analysis were performed using a variance components procedure implemented in SOLAR software. Results: The heritability estimates were 0.62 for BMI, 0.73 for BSA, 0.40 for WHR, and 0.38 for trunk fat mass as percentage of body weight. Using a bivariate genetic model, we observed significant genetic correlations between BMI and other obesity‐related traits (all p < 0.01). Evidence for univariate linkage was observed at 252 to approximately 267 cM on chromosome 2 for three obesity‐related traits (except for WHR) and at 163 to approximately 167 cM on chromosome 5 for BMI and BSA, with the maximum logarithm of the odds ratio score of 3.12 (empirical p value, 0.002) for BSA on chromosome 2. Use of the bivariate linkage model yielded an additional peak (logarithm of the odds ratio = 3.25, empirical p value, 0.002) at 25 cM on chromosome 7 for the pair of BMI and BSA. Discussion: The evidence for linkage on chromosomes 2q36‐37 and 5q36 is supported both by univariate and bivariate analysis, and an additional linkage peak at 7p15 was identified by the bivariate model. This suggests that use of the bivariate model provides additional information to identify linkage of genes responsible for obesity‐related traits.     

Classification of the flea families (Siphonaptera): I. Family Hystrichopsyllidae (Part 5)

Based on analysis of homologous character states and considering the molecular-biological data (Whiting et al., 2008), phylogenetic relationships of the tribes and subfamilies of the family Hystrichopsyllidae are discussed. In some cases, homologous states of the skeleton characters mark the clades revealed by the moleculargenetic analysis, but are shared by taxa from other clades. In contrast to the molecular-genetic data, morphological characters indicate the phylogenetic integrity of the family Hystrichopsyllidae. Morphological characters depict the subfamily Anomiopsyllinae as a monophyletic taxon (having synapomorphic states of the metaphragma, metasternite, and the mesosternal apodeme) closest to the subfamilies Neopsyllinae and Rhadinopsyllinae. The subfamilies Neopsyllinae, Rhadinopsyllinae, and Stenoponiinae have a non-thickened metasternite; the former two subfamilies also have in common a similar structure of articulation of the digitoid with the clasper, type of the metaphragma modification, and the presence of the sclerotized central sclerite. Homologous modifications of the metaphragma are also present in fleas of the subfamily Stenoponiinae. Close to this group are the subfamily Hystrichopsyllinae whose representatives also possess non-thickened metasternal apodemes, and the subfamily Listropsyllinae with its frontal sclerotized tubercle being a specialized modification of the frontal sclerotized fold. A specific feature shared by fleas of the subfamilies Hystrichopsyllinae and Listropsyllinae is the presence of the metasternal furca with high sharp processes and a high medial ridge. The closeness of these taxa is supported by the results of molecular-genetic analysis. The subfamilies Doratopsyllinae and Ctenophthalminae (tribes Ctenophthalmini and Carterettini) are united by the type of the attachment of the mesopleural rod to the special ridge at the upper margin of the mesopleuron. According to the molecular-genetic data, the tribe Neotyphloceratini is related to these subfamilies, even though its members have no ridge on the mesopleuron. The similarity in the structure of the furca (the presence of high dorsal processes with rounded apices and a high median ridge) and in the length ratio of the fulcrum lobes relates the subfamilies Ctenophthalminae and Dinopsyllinae.     

Classification of the flea families (Siphonaptera): II. Family hystrichopsyllidae (Part 4)

Distribution of the ancestral, homoiologous, and convergent character states over the tagmata and morpho-functional complexes of the flea body in nine subfamilies of the Hystrichopsyllidae is analyzed. The analysis is based upon the states of 111 characters of 73 structures of 3 tagmata in the adult flea body. The homoiologous states (those arising in parallel in close flea infraorders) comprise 35%, the ancestral (the least specialized) ones, 16%, and the convergent ones, 13% of the total number of character states of all the 10 types. The greatest numbers of the ancestral character states in the Hystrichopsyllidae are found in the mesothorax (22.8%) and aedeagus (21.1%); the metathorax reveals 19.3%, and the head, 17.5% of the ancestral character states. The greatest number of homoiologous character states, 34.1% of the total number, is observed in the mesothoracal segment. Smaller fractions of the homoiologous character states are found in the head (24.6%) and metathorax (17.5%). Those character states which arise in the phylogenetically remote infraorders are considered convergent. The greatest number of convergent character states in the Hystrichopsyllidae (55.1%) is observed in the structure of the aedeagus.